Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies

Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whet...
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Autor*in:	Bálint Mészáros [verfasserIn] Borbála Hajdu-Soltész [verfasserIn] András Zeke [verfasserIn] Zsuzsanna Dosztányi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification

Übergeordnetes Werk:	In: Biomolecules - MDPI AG, 2013, 11(2021), 3, p 381
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:3, p 381

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biom11030381

Katalog-ID:	DOAJ057028850

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allfields	10.3390/biom11030381 doi (DE-627)DOAJ057028850 (DE-599)DOAJcf6063ae62914c77a4380e75ba280477 DE-627 ger DE-627 rakwb eng QR1-502 Bálint Mészáros verfasserin aut Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options. intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification Microbiology Borbála Hajdu-Soltész verfasserin aut András Zeke verfasserin aut Zsuzsanna Dosztányi verfasserin aut In Biomolecules MDPI AG, 2013 11(2021), 3, p 381 (DE-627)735688915 (DE-600)2701262-1 2218273X nnns volume:11 year:2021 number:3, p 381 https://doi.org/10.3390/biom11030381 kostenfrei https://doaj.org/article/cf6063ae62914c77a4380e75ba280477 kostenfrei https://www.mdpi.com/2218-273X/11/3/381 kostenfrei https://doaj.org/toc/2218-273X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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 11 2021 3, p 381
spelling	10.3390/biom11030381 doi (DE-627)DOAJ057028850 (DE-599)DOAJcf6063ae62914c77a4380e75ba280477 DE-627 ger DE-627 rakwb eng QR1-502 Bálint Mészáros verfasserin aut Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options. intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification Microbiology Borbála Hajdu-Soltész verfasserin aut András Zeke verfasserin aut Zsuzsanna Dosztányi verfasserin aut In Biomolecules MDPI AG, 2013 11(2021), 3, p 381 (DE-627)735688915 (DE-600)2701262-1 2218273X nnns volume:11 year:2021 number:3, p 381 https://doi.org/10.3390/biom11030381 kostenfrei https://doaj.org/article/cf6063ae62914c77a4380e75ba280477 kostenfrei https://www.mdpi.com/2218-273X/11/3/381 kostenfrei https://doaj.org/toc/2218-273X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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 11 2021 3, p 381
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allfieldsGer	10.3390/biom11030381 doi (DE-627)DOAJ057028850 (DE-599)DOAJcf6063ae62914c77a4380e75ba280477 DE-627 ger DE-627 rakwb eng QR1-502 Bálint Mészáros verfasserin aut Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options. intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification Microbiology Borbála Hajdu-Soltész verfasserin aut András Zeke verfasserin aut Zsuzsanna Dosztányi verfasserin aut In Biomolecules MDPI AG, 2013 11(2021), 3, p 381 (DE-627)735688915 (DE-600)2701262-1 2218273X nnns volume:11 year:2021 number:3, p 381 https://doi.org/10.3390/biom11030381 kostenfrei https://doaj.org/article/cf6063ae62914c77a4380e75ba280477 kostenfrei https://www.mdpi.com/2218-273X/11/3/381 kostenfrei https://doaj.org/toc/2218-273X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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 11 2021 3, p 381
allfieldsSound	10.3390/biom11030381 doi (DE-627)DOAJ057028850 (DE-599)DOAJcf6063ae62914c77a4380e75ba280477 DE-627 ger DE-627 rakwb eng QR1-502 Bálint Mészáros verfasserin aut Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options. intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification Microbiology Borbála Hajdu-Soltész verfasserin aut András Zeke verfasserin aut Zsuzsanna Dosztányi verfasserin aut In Biomolecules MDPI AG, 2013 11(2021), 3, p 381 (DE-627)735688915 (DE-600)2701262-1 2218273X nnns volume:11 year:2021 number:3, p 381 https://doi.org/10.3390/biom11030381 kostenfrei https://doaj.org/article/cf6063ae62914c77a4380e75ba280477 kostenfrei https://www.mdpi.com/2218-273X/11/3/381 kostenfrei https://doaj.org/toc/2218-273X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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 11 2021 3, p 381
language	English
source	In Biomolecules 11(2021), 3, p 381 volume:11 year:2021 number:3, p 381
sourceStr	In Biomolecules 11(2021), 3, p 381 volume:11 year:2021 number:3, p 381
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification Microbiology
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container_title	Biomolecules
authorswithroles_txt_mv	Bálint Mészáros @@aut@@ Borbála Hajdu-Soltész @@aut@@ András Zeke @@aut@@ Zsuzsanna Dosztányi @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Bálint Mészáros
spellingShingle	Bálint Mészáros misc QR1-502 misc intrinsically disordered regions misc protein modules misc short linear motifs misc molecular switches misc cancer genomics misc driver gene identification misc Microbiology Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
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topic_title	QR1-502 Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies intrinsically disordered regions protein modules short linear motifs molecular switches cancer genomics driver gene identification
topic	misc QR1-502 misc intrinsically disordered regions misc protein modules misc short linear motifs misc molecular switches misc cancer genomics misc driver gene identification misc Microbiology
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title	Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
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title_full	Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
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title_sort	mutations of intrinsically disordered protein regions can drive cancer but lack therapeutic strategies
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title_auth	Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
abstract	Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.
abstractGer	Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.
abstract_unstemmed	Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.
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title_short	Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
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