MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation

Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma t...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Rosner, Marsha Rich [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2007

Schlagwörter:	Taxol Spindle Assembly Checkpoint Spindle Checkpoint Passenger Protein Mitotic Spindle Assembly Checkpoint

Anmerkung:	© Rosner; licensee BioMed Central Ltd. 2007

Übergeordnetes Werk:	Enthalten in: Cell division - London : BioMed Central, 2006, 2(2007), 1 vom: 10. Jan.
Übergeordnetes Werk:	volume:2 ; year:2007 ; number:1 ; day:10 ; month:01

Links:	Volltext

DOI / URN:	10.1186/1747-1028-2-1

Katalog-ID:	SPR029413133

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520			\|a Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint.
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Indexfelder

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allfields	10.1186/1747-1028-2-1 doi (DE-627)SPR029413133 (SPR)1747-1028-2-1-e DE-627 ger DE-627 rakwb eng Rosner, Marsha Rich verfasserin aut MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rosner; licensee BioMed Central Ltd. 2007 Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213 Enthalten in Cell division London : BioMed Central, 2006 2(2007), 1 vom: 10. Jan. (DE-627)512300607 (DE-600)2236097-9 1747-1028 nnns volume:2 year:2007 number:1 day:10 month:01 https://dx.doi.org/10.1186/1747-1028-2-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2007 1 10 01
spelling	10.1186/1747-1028-2-1 doi (DE-627)SPR029413133 (SPR)1747-1028-2-1-e DE-627 ger DE-627 rakwb eng Rosner, Marsha Rich verfasserin aut MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rosner; licensee BioMed Central Ltd. 2007 Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213 Enthalten in Cell division London : BioMed Central, 2006 2(2007), 1 vom: 10. Jan. (DE-627)512300607 (DE-600)2236097-9 1747-1028 nnns volume:2 year:2007 number:1 day:10 month:01 https://dx.doi.org/10.1186/1747-1028-2-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2007 1 10 01
allfields_unstemmed	10.1186/1747-1028-2-1 doi (DE-627)SPR029413133 (SPR)1747-1028-2-1-e DE-627 ger DE-627 rakwb eng Rosner, Marsha Rich verfasserin aut MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rosner; licensee BioMed Central Ltd. 2007 Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213 Enthalten in Cell division London : BioMed Central, 2006 2(2007), 1 vom: 10. Jan. (DE-627)512300607 (DE-600)2236097-9 1747-1028 nnns volume:2 year:2007 number:1 day:10 month:01 https://dx.doi.org/10.1186/1747-1028-2-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2007 1 10 01
allfieldsGer	10.1186/1747-1028-2-1 doi (DE-627)SPR029413133 (SPR)1747-1028-2-1-e DE-627 ger DE-627 rakwb eng Rosner, Marsha Rich verfasserin aut MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rosner; licensee BioMed Central Ltd. 2007 Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213 Enthalten in Cell division London : BioMed Central, 2006 2(2007), 1 vom: 10. Jan. (DE-627)512300607 (DE-600)2236097-9 1747-1028 nnns volume:2 year:2007 number:1 day:10 month:01 https://dx.doi.org/10.1186/1747-1028-2-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2007 1 10 01
allfieldsSound	10.1186/1747-1028-2-1 doi (DE-627)SPR029413133 (SPR)1747-1028-2-1-e DE-627 ger DE-627 rakwb eng Rosner, Marsha Rich verfasserin aut MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rosner; licensee BioMed Central Ltd. 2007 Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213 Enthalten in Cell division London : BioMed Central, 2006 2(2007), 1 vom: 10. Jan. (DE-627)512300607 (DE-600)2236097-9 1747-1028 nnns volume:2 year:2007 number:1 day:10 month:01 https://dx.doi.org/10.1186/1747-1028-2-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2007 1 10 01
language	English
source	Enthalten in Cell division 2(2007), 1 vom: 10. Jan. volume:2 year:2007 number:1 day:10 month:01
sourceStr	Enthalten in Cell division 2(2007), 1 vom: 10. Jan. volume:2 year:2007 number:1 day:10 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Taxol Spindle Assembly Checkpoint Spindle Checkpoint Passenger Protein Mitotic Spindle Assembly Checkpoint
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container_title	Cell division
authorswithroles_txt_mv	Rosner, Marsha Rich @@aut@@
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author	Rosner, Marsha Rich
spellingShingle	Rosner, Marsha Rich misc Taxol misc Spindle Assembly Checkpoint misc Spindle Checkpoint misc Passenger Protein misc Mitotic Spindle Assembly Checkpoint MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation
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topic_title	MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation Taxol (dpeaa)DE-He213 Spindle Assembly Checkpoint (dpeaa)DE-He213 Spindle Checkpoint (dpeaa)DE-He213 Passenger Protein (dpeaa)DE-He213 Mitotic Spindle Assembly Checkpoint (dpeaa)DE-He213
topic	misc Taxol misc Spindle Assembly Checkpoint misc Spindle Checkpoint misc Passenger Protein misc Mitotic Spindle Assembly Checkpoint
topic_unstemmed	misc Taxol misc Spindle Assembly Checkpoint misc Spindle Checkpoint misc Passenger Protein misc Mitotic Spindle Assembly Checkpoint
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title	MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation
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title_full	MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation
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title_sort	map kinase meets mitosis: a role for raf kinase inhibitory protein in spindle checkpoint regulation
title_auth	MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation
abstract	Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. © Rosner; licensee BioMed Central Ltd. 2007
abstractGer	Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. © Rosner; licensee BioMed Central Ltd. 2007
abstract_unstemmed	Abstract Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with poor prognosis for breast, prostate and melanoma tumors but the mechanism is unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity, and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP kinase signaling during the G1, S or G2 phases of the cell cycle that activates checkpoints and induces arrest or senescence, loss of RKIP during M phase leads to bypass of the spindle assembly checkpoint and the generation of chromosomal abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior to cell division. Furthermore, these data highlight the need for precise titration of the MAP kinase signal to ensure the integrity of the spindle assembly process and provide a mechanism for generating genomic instability in tumors. Finally, these results raise the possibility that RKIP status in tumors could influence the efficacy of treatments such as poisons that stimulate the Aurora B-dependent spindle assembly checkpoint. © Rosner; licensee BioMed Central Ltd. 2007
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title_short	MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation
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MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation

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