negative regulation of fatty acid biosynthetic process / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex ...negative regulation of fatty acid biosynthetic process / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / cullin family protein binding / viral release from host cell / ectopic germ cell programmed cell death / positive regulation of viral genome replication / positive regulation of gluconeogenesis / proteasomal protein catabolic process / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / regulation of circadian rhythm / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Wntシグナル経路 / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / protein polyubiquitination / positive regulation of protein catabolic process / cellular response to UV / rhythmic process / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / site of double-strand break / Neddylation / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / damaged DNA binding / chromosome, telomeric region / protein ubiquitination / DNA修復 / apoptotic process / DNA damage response / protein-containing complex binding / 核小体 / negative regulation of apoptotic process / protein-containing complex / DNA binding / extracellular space / extracellular exosome / 核質 / 細胞核 / 細胞質 類似検索 - 分子機能
DDB1- and CUL4-associated factor 8-like / DET1- and DDB1-associated protein 1, N-terminal / DET1- and DDB1-associated protein 1 / Det1 complexing ubiquitin ligase / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / CPSF A subunit region / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. ...DDB1- and CUL4-associated factor 8-like / DET1- and DDB1-associated protein 1, N-terminal / DET1- and DDB1-associated protein 1 / Det1 complexing ubiquitin ligase / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / CPSF A subunit region / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40リピート / WD40リピート / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性
DNA damage-binding protein 1 / DDB1- and CUL4-associated factor 5 / DET1- and DDB1-associated protein 1 類似検索 - 構成要素
ジャーナル: Nature / 年: 2024 タイトル: Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF. 著者: Sandi Radko-Juettner / Hong Yue / Jacquelyn A Myers / Raymond D Carter / Alexis N Robertson / Priya Mittal / Zhexin Zhu / Baranda S Hansen / Katherine A Donovan / Moritz Hunkeler / Wojciech ...著者: Sandi Radko-Juettner / Hong Yue / Jacquelyn A Myers / Raymond D Carter / Alexis N Robertson / Priya Mittal / Zhexin Zhu / Baranda S Hansen / Katherine A Donovan / Moritz Hunkeler / Wojciech Rosikiewicz / Zhiping Wu / Meghan G McReynolds / Shourya S Roy Burman / Anna M Schmoker / Nada Mageed / Scott A Brown / Robert J Mobley / Janet F Partridge / Elizabeth A Stewart / Shondra M Pruett-Miller / Behnam Nabet / Junmin Peng / Nathanael S Gray / Eric S Fischer / Charles W M Roberts / 要旨: Whereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to ...Whereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes. Here, to generate mechanistic insights into the consequences of SMARCB1 mutation and to identify vulnerabilities, we contributed 14 SMARCB1-mutant cell lines to a near genome-wide CRISPR screen as part of the Cancer Dependency Map Project. We report that the little-studied gene DDB1-CUL4-associated factor 5 (DCAF5) is required for the survival of SMARCB1-mutant cancers. We show that DCAF5 has a quality-control function for SWI/SNF complexes and promotes the degradation of incompletely assembled SWI/SNF complexes in the absence of SMARCB1. After depletion of DCAF5, SMARCB1-deficient SWI/SNF complexes reaccumulate, bind to target loci and restore SWI/SNF-mediated gene expression to levels that are sufficient to reverse the cancer state, including in vivo. Consequently, cancer results not from the loss of SMARCB1 function per se, but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of ubiquitin-mediated quality-control factors may effectively reverse the malignant state of some cancers driven by disruption of tumour suppressor complexes.