Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist
Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is...
Ausführliche Beschreibung
Autor*in: |
Ma, Aiqing [verfasserIn] Dai, Xianhua [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Interdisciplinary sciences - Berlin : Springer, 2009, 11(2019), 4 vom: 20. Juni, Seite 679-690 |
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Übergeordnetes Werk: |
volume:11 ; year:2019 ; number:4 ; day:20 ; month:06 ; pages:679-690 |
Links: |
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DOI / URN: |
10.1007/s12539-019-00332-z |
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Katalog-ID: |
SPR026062186 |
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520 | |a Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. | ||
650 | 4 | |a Single-stranded breaks (SSBs) |7 (dpeaa)DE-He213 | |
650 | 4 | |a Double-stranded breaks (DSBs) |7 (dpeaa)DE-He213 | |
650 | 4 | |a P53 response |7 (dpeaa)DE-He213 | |
650 | 4 | |a Apoptosis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Parameter sensitivity analysis |7 (dpeaa)DE-He213 | |
700 | 1 | |a Dai, Xianhua |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Interdisciplinary sciences |d Berlin : Springer, 2009 |g 11(2019), 4 vom: 20. Juni, Seite 679-690 |w (DE-627)599241713 |w (DE-600)2493085-4 |x 1867-1462 |7 nnns |
773 | 1 | 8 | |g volume:11 |g year:2019 |g number:4 |g day:20 |g month:06 |g pages:679-690 |
856 | 4 | 0 | |u https://dx.doi.org/10.1007/s12539-019-00332-z |z lizenzpflichtig |3 Volltext |
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10.1007/s12539-019-00332-z doi (DE-627)SPR026062186 (SPR)s12539-019-00332-z-e DE-627 ger DE-627 rakwb eng 004 ASE Ma, Aiqing verfasserin aut Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 Dai, Xianhua verfasserin aut Enthalten in Interdisciplinary sciences Berlin : Springer, 2009 11(2019), 4 vom: 20. Juni, Seite 679-690 (DE-627)599241713 (DE-600)2493085-4 1867-1462 nnns volume:11 year:2019 number:4 day:20 month:06 pages:679-690 https://dx.doi.org/10.1007/s12539-019-00332-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 11 2019 4 20 06 679-690 |
spelling |
10.1007/s12539-019-00332-z doi (DE-627)SPR026062186 (SPR)s12539-019-00332-z-e DE-627 ger DE-627 rakwb eng 004 ASE Ma, Aiqing verfasserin aut Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 Dai, Xianhua verfasserin aut Enthalten in Interdisciplinary sciences Berlin : Springer, 2009 11(2019), 4 vom: 20. Juni, Seite 679-690 (DE-627)599241713 (DE-600)2493085-4 1867-1462 nnns volume:11 year:2019 number:4 day:20 month:06 pages:679-690 https://dx.doi.org/10.1007/s12539-019-00332-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 11 2019 4 20 06 679-690 |
allfields_unstemmed |
10.1007/s12539-019-00332-z doi (DE-627)SPR026062186 (SPR)s12539-019-00332-z-e DE-627 ger DE-627 rakwb eng 004 ASE Ma, Aiqing verfasserin aut Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 Dai, Xianhua verfasserin aut Enthalten in Interdisciplinary sciences Berlin : Springer, 2009 11(2019), 4 vom: 20. Juni, Seite 679-690 (DE-627)599241713 (DE-600)2493085-4 1867-1462 nnns volume:11 year:2019 number:4 day:20 month:06 pages:679-690 https://dx.doi.org/10.1007/s12539-019-00332-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 11 2019 4 20 06 679-690 |
allfieldsGer |
10.1007/s12539-019-00332-z doi (DE-627)SPR026062186 (SPR)s12539-019-00332-z-e DE-627 ger DE-627 rakwb eng 004 ASE Ma, Aiqing verfasserin aut Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 Dai, Xianhua verfasserin aut Enthalten in Interdisciplinary sciences Berlin : Springer, 2009 11(2019), 4 vom: 20. Juni, Seite 679-690 (DE-627)599241713 (DE-600)2493085-4 1867-1462 nnns volume:11 year:2019 number:4 day:20 month:06 pages:679-690 https://dx.doi.org/10.1007/s12539-019-00332-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 11 2019 4 20 06 679-690 |
allfieldsSound |
10.1007/s12539-019-00332-z doi (DE-627)SPR026062186 (SPR)s12539-019-00332-z-e DE-627 ger DE-627 rakwb eng 004 ASE Ma, Aiqing verfasserin aut Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 Dai, Xianhua verfasserin aut Enthalten in Interdisciplinary sciences Berlin : Springer, 2009 11(2019), 4 vom: 20. Juni, Seite 679-690 (DE-627)599241713 (DE-600)2493085-4 1867-1462 nnns volume:11 year:2019 number:4 day:20 month:06 pages:679-690 https://dx.doi.org/10.1007/s12539-019-00332-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 11 2019 4 20 06 679-690 |
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Enthalten in Interdisciplinary sciences 11(2019), 4 vom: 20. Juni, Seite 679-690 volume:11 year:2019 number:4 day:20 month:06 pages:679-690 |
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Ma, Aiqing @@aut@@ Dai, Xianhua @@aut@@ |
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P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single-stranded breaks (SSBs)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Double-stranded breaks (DSBs)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">P53 response</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Apoptosis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Parameter sensitivity analysis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dai, Xianhua</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Interdisciplinary sciences</subfield><subfield code="d">Berlin : Springer, 2009</subfield><subfield code="g">11(2019), 4 vom: 20. 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|
author |
Ma, Aiqing |
spellingShingle |
Ma, Aiqing ddc 004 misc Single-stranded breaks (SSBs) misc Double-stranded breaks (DSBs) misc P53 response misc Apoptosis misc Parameter sensitivity analysis Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist |
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Ma, Aiqing |
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004 ASE Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist Single-stranded breaks (SSBs) (dpeaa)DE-He213 Double-stranded breaks (DSBs) (dpeaa)DE-He213 P53 response (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Parameter sensitivity analysis (dpeaa)DE-He213 |
topic |
ddc 004 misc Single-stranded breaks (SSBs) misc Double-stranded breaks (DSBs) misc P53 response misc Apoptosis misc Parameter sensitivity analysis |
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ddc 004 misc Single-stranded breaks (SSBs) misc Double-stranded breaks (DSBs) misc P53 response misc Apoptosis misc Parameter sensitivity analysis |
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ddc 004 misc Single-stranded breaks (SSBs) misc Double-stranded breaks (DSBs) misc P53 response misc Apoptosis misc Parameter sensitivity analysis |
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Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist |
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Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist |
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Ma, Aiqing |
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Ma, Aiqing Dai, Xianhua |
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Elektronische Aufsätze |
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Ma, Aiqing |
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exploring the influence of parameters on the p53 response when single-stranded breaks and double-stranded breaks coexist |
title_auth |
Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist |
abstract |
Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. |
abstractGer |
Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. |
abstract_unstemmed |
Abstract The p53 response to DNA damage is closely related to cell fate decisions. P53 preferentially responds to single-stranded breaks (SSBs) exhibiting a graded response when single-stranded breaks (SSBs) and double-stranded breaks (DSBs) coexist. However, how p53 natural preferential response is affected by kinetic parameters remains to be elucidated. Here, based on the hybrid model I, we computationally searched all the parameters and parameter combinations in the parameter space to identify those that could alter the natural preferential response of p53 when SSBs and DSBs coexist. Firstly, when a single parameter is changed, the parameters that can alter graded response to produce p53 pulse response are production rate of ATM- and Rad3-related kinase(ATR) (beta2), ATR degradation rate (alf2) and ATR-dependent p53 production rate (beta31). Secondly, when double parameters are changed, the combinations of beta2/alf2/beta31 and any other parameters are capable of altering the p53 natural preferential response, and the combination of ataxia-telangiectasia mutated kinase (ATM)-dependent p53 production rate (beta3) and Wip1-dependent p53 degradation rate (alf35) is also capable of altering the p53 natural preferential response. Thirdly, we analyzed the sensitivity of both pulse amplitude and apoptosis to kinetic parameters. We find that pulse amplitude is most sensitive to ATM-dependent p53 production rate (beta3), and apoptosis is more sensitive to damage-dependent ATM production rate (beta1), wip1-dependent ATM degradation rate (alf15), wip1 production rate (beta5) and wip1 degradation rate (alf5). What is more, the smaller the value of alf15/beta5 or the larger the value of beta1/alf5, the more susceptible the cells are to apoptosis. These results provide clues to design more effective and less toxic targeted treatments for cancer. |
collection_details |
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container_issue |
4 |
title_short |
Exploring the Influence of Parameters on the p53 Response When Single-Stranded Breaks and Double-Stranded Breaks Coexist |
url |
https://dx.doi.org/10.1007/s12539-019-00332-z |
remote_bool |
true |
author2 |
Dai, Xianhua |
author2Str |
Dai, Xianhua |
ppnlink |
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hochschulschrift_bool |
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doi_str |
10.1007/s12539-019-00332-z |
up_date |
2024-07-03T18:39:42.093Z |
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score |
7.4007807 |