The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and Is a Critical Regulator of Gene Expression
Helen Yu,Nazar Mashtalir,Salima Daou,Ian Hammond-Martel,Julie Ross,Guangchao Sui,Gerald W. Hart,Frank J. Rauscher,Elliot Drobetsky,Eric Milot,Yang Shi,El Bachir Affar +11 more
TLDR
The findings establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and shed light on a novel mechanism of transcription regulation involving ubiquitin signaling.Abstract:
The candidate tumor suppressor BAP1 is a deubiquitinating enzyme (DUB) involved in the regulation of cell proliferation, although the molecular mechanisms governing its function remain poorly defined. BAP1 was recently shown to interact with and deubiquitinate the transcriptional regulator host cell factor 1 (HCF-1). Here we show that BAP1 assembles multiprotein complexes containing numerous transcription factors and cofactors, including HCF-1 and the transcription factor Yin Yang 1 (YY1). Through its coiled-coil motif, BAP1 directly interacts with the zinc fingers of YY1. Moreover, HCF-1 interacts with the middle region of YY1 encompassing the glycine-lysine-rich domain and is essential for the formation of a ternary complex with YY1 and BAP1 in vivo. BAP1 activates transcription in an enzymatic-activity-dependent manner and regulates the expression of a variety of genes involved in numerous cellular processes. We further show that BAP1 and HCF-1 are recruited by YY1 to the promoter of the cox7c gene, which encodes a mitochondrial protein used here as a model of BAP1-activated gene expression. Our findings (i) establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and (ii) shed light on a novel mechanism of transcription regulation involving ubiquitin signaling.read more
Citations
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BAP1 loss defines a new class of renal cell carcinoma
Samuel Peña-Llopis,Silvia Vega-Rubin-de-Celis,Silvia Vega-Rubin-de-Celis,Arnold Liao,Nan Leng,Andrea Pavia-Jimenez,Andrea Pavia-Jimenez,Shanshan Wang,Shanshan Wang,Toshinari Yamasaki,Toshinari Yamasaki,Leah Zhrebker,Leah Zhrebker,Sharanya Sivanand,Sharanya Sivanand,Patrick Spence,Patrick Spence,Lisa N. Kinch,Tina Hambuch,Suneer Jain,Yair Lotan,Vitaly Margulis,Arthur I. Sagalowsky,Pia Banerji Summerour,Wareef Kabbani,S. W Wendy Wong,Nick V. Grishin,Marc Laurent,Xian Jin Xie,Christian D. Haudenschild,Mark T. Ross,David R. Bentley,Payal Kapur,James Brugarolas +33 more
TL;DR: The results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
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BAP1 and cancer
TL;DR: Findings indicate that germline BAP1 mutations cause a novel cancer syndrome that is characterized by the onset at an early age of benign melanocytic skin tumours with mutated B AP1, and later in life by a high incidence of mesothelioma, uveal melanoma, cutaneous melanoma and possibly additional cancers.
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BAP1 links metabolic regulation of ferroptosis to tumour suppression.
Yilei Zhang,Jiejun Shi,Xiaoguang Liu,Li Feng,Zihua Gong,Zihua Gong,Pranavi Koppula,Pranavi Koppula,Kapil Sirohi,Xu Li,Xu Li,Yongkun Wei,Hyemin Lee,Li Zhuang,Gang Chen,Zhen Dong Xiao,Zhen Dong Xiao,Mien Chie Hung,Junjie Chen,Junjie Chen,Peng Huang,Peng Huang,Wei Li,Boyi Gan,Boyi Gan +24 more
TL;DR: It is shown that BAP1 suppresses SLC7A11 expression and cystine uptake, thereby promoting ferroptosis and inhibiting tumour growth and uncovering a previously unappreciated epigenetic mechanism coupling ferroPTosis to tumour suppression.
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Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments
Pouya Kheradpour,Manolis Kellis +1 more
TL;DR: A systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools, providing a principled way for choosing between motif variants found in the Literature and for flagging potentially problematic data sets.
Journal ArticleDOI
Integrative Molecular Characterization of Malignant Pleural Mesothelioma
Julija Hmeljak,Francisco Sanchez-Vega,Katherine A. Hoadley,Juliann Shih,Chip Stewart,David I. Heiman,Patrick S. Tarpey,Ludmila Danilova,Esther Drill,Ewan A. Gibb,Reanne Bowlby,Rupa S. Kanchi,Hatice U. Osmanbeyoglu,Yoshitaka Sekido,Jumpei Takeshita,Yulia Newton,Kiley Graim,Manaswi Gupta,Lixia Diao,David L Gibbs,Vesteinn Thorsson,Lisa Iype,Havish S. Kantheti,David T. Severson,Gloria Ravegnini,Patrice Desmeules,Achim A. Jungbluth,William D. Travis,Sanja Dacic,Lucian R. Chirieac,Françoise Galateau-Sallé,Junya Fujimoto,Aliya N. Husain,Henrique César Santejo Silveira,Valerie W. Rusch,Robert C. Rintoul,Harvey I. Pass,Hedy L. Kindler,Marjorie G. Zauderer,David J. Kwiatkowski,Raphael Bueno,Anne S. Tsao,Jenette Creaney,Tara M. Lichtenberg,Kristen M. Leraas,Jay Bowen,Ina Felau,Jean C. Zenklusen,Rehan Akbani,Andrew D. Cherniack,Lauren Averett Byers,Michael S. Noble,Jonathan A. Fletcher,Gordon Robertson,Ronglai Shen,Hiroyuki Aburatani,Bruce W. S. Robinson,Peter J. Campbell,Marc Ladanyi +58 more
TL;DR: A comprehensive integrated genomic study of 74 MPMs provided a deeper understanding of histology-independent determinants of aggressive behavior, defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.
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