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USP14-Dependent IGF1R Aggravates High Glucose-Induced Diabetic Retinopathy by Upregulating bap1

APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY 2025年 1-16页

作者： Yu, Li Zheng, Xia Wu, Yan Ge, Kui First Peoples Hosp Dept Ophthalmol 1 Zhifang Cultural Ave Wuhan 430200 Hubei Peoples R China

Diabeticretinopathy (DR) is a microvascular complication of diabetes. Insulin-like growth factor 1 receptor (IGF1R) has been implicated in the pathogenesis of DR;however, the underlying mechanism remains unclear. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess IGF1R mRNA expression. Western blotting assays were performed to analyze the protein expression of IGF1R, ubiquitin-specific peptidase 14 (USP14), and BRCA1-associated protein 1 (bap1). Cell viability, apoptosis, interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) levels were analyzed using cell counting kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Fluorescent microscopy and flow cytometry were performed for reactive oxygen species (ROS) level assessment, and colorimetric assays for iron (Fe2+) and glutathione (GSH) levels. Co-immunoprecipitation assays and/or colocalization techniques were employed to validate the association of IGF1R with USP14 and bap1. Treatment with high glucose (HG) increased the protein expression of IGF1R, USP14, and bap1 in ARPE-19 cells. Silencing of IGF1R mitigated HG-induced apoptosis, inflammatory response, and ferroptosis in ARPE-19 cells. USP14 was found to stabilize IGF1R protein expression through deubiquitination. Overexpression of USP14 exacerbated HG-induced cellular injury, whereas silencing of USP14 protected ARPE-19 cells by reducing IGF1R expression. Interaction between IGF1R and bap1 was confirmed in ARPE-19 cells and IGF1R silencing protected cells from HG-induced injury by regulating bap1 expression. Thus, USP14-dependent regulation of IGF1R expression and its interaction with bap1 play a crucial role in the pathogenesis of high glucose-induced diabetic retinopathy.

关键词： Diabetic retinopathy IGF1R USP14 bap1 Ferroptosis

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Loss of histone deubiquitinase bap1 triggers anti-tumor immunity

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CELLULAR ONCOLOGY 2025年第1期48卷 183-203页

作者： Chang, Hong Li, Mingxia Zhang, Linlin Li, Meng Ong, Swee Hoe Zhang, Zhiwei Zheng, Jie Xu, Xiang Zhang, Yu Wang, Jing Liu, Xingjie Li, Kairui Luo, Yao Wang, Haiyun Miao, Zhichao Chen, Xi Zha, Jie Yu, Yong Tongji Univ Tongji Hosp Frontier Sci Ctr Stem Cell Res Sch Life Sci & Technol 1239 Siping Rd Shanghai 200092 Peoples R China Xiamen Univ Affiliated Hosp 1 Dept Hematol Xiamen Peoples R China Xiamen Univ Inst Hematol Sch Med Xiamen Peoples R China Key Lab Xiamen Diag & Treatment Hematol Malignancy Xiamen Peoples R China Wellcome Sanger Inst Cambridge CB10 1HH England Tongji Univ Shanghai Peoples Hosp Affiliated 4 Translat Res Inst Brain & Brain Like Intelligence Sch Med Shanghai 200081 Peoples R China Guangzhou Med Univ GIBH Joint Sch Life Sci Guangdong Hong Kong Macau Joint Lab Cell Fate Regu Guangzhou Lab Hong Kong Peoples R China Southern Univ Sci & Technol Dept Biol 1088 Xueyuan Ave Shenzhen 518055 Peoples R China

PurposeImmunotherapy using PD-L1 blockade is effective in only a small group of cancer patients, and resistance is common. This emphasizes the importance of understanding the mechanisms of cancer immune evasion and *** genome-scale CRISPR-Cas9 screen identified bap1 as a regulator of PD-L1 expression. To measure tumor size and survival, tumor cells were subcutaneously injected into both syngeneic WT mice and immunocompromised mice. The phenotypic and transcriptional characteristics of bap1-deleted tumors were examined using flow cytometry, RNA-seq, and CUT&Tag-seq *** found that loss of histone deubiquitinase bap1 in cancer cells activates a cDC1-CD8+ T cell-dependent anti-tumor immunity. The absence of bap1 leads to an increase in genes associated with anti-tumor immune response and a decrease in genes related to immune evasion. As a result, the tumor microenvironment becomes inflamed, with more cDC1 cells and effector CD8+ T cells, but fewer neutrophils and regulatory T cells. We also found that the elimination of bap1-deleted tumors depends on the tumor MHCI molecule and Fas-mediated CD8+ T cell cytotoxicity. Our analysis of TCGA data further supports these findings, showing a reverse correlation between bap1 expression and mRNA signatures of activated DCs and T-cell cytotoxicity in various human *** histone deubiquitinase bap1 could be used as a biomarker for tumor stratification and as a potential therapeutic target for cancer immunotherapies.

关键词： bap1 Tumor microenvironment PD-L1 Anti-tumor immunity

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The SIRT6/bap1/xCT signaling axis mediates ferroptosis in cisplatin-induced AKI

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CELLULAR SIGNALLING 2025年 125卷 111479页

作者： Yang, Songyuan Chen, Lijia Din, Shikuan Ye, Zehua Zhou, Xiangjun Cheng, Fan Li, Wei Wuhan Univ Dept Urol Renmin Hosp Wuhan 430060 Peoples R China Wuhan Univ Dept Neurol Renmin Hosp Wuhan 430060 Peoples R China Wuhan Univ Dept Anesthesiol Renmin Hosp Wuhan 430060 Peoples R China

Background: Cisplatin is extensively utilized in clinical settings for treating solid tumors;However, its use is restricted because of the kidney damage caused by side effects. Moreover, currently, no effective medications have been approved to prevent or treat acute kidney injury induced by cisplatin. Our research indicates that sirtuin 6 (SIRT6) can inhibit ferroptosis induced by cisplatin, and the use of SIRT6 agonists can alleviate acute kidney injury caused by cisplatin. Methods: An animal model of cisplatin-induced acute kidney injury (AKI) was established, followed by RNA sequencing to identify potential differentially expressed genes (DEGs) and associated pathways. To explore the role of SIRT6 in this model, SIRT6 knockout mice were generated, and recombinant adeno-associated virus was employed to achieve SIRT6 overexpression in the mice. In vitro, cells were cultured in a cisplatin-containing medium to establish a cisplatin-induced cell model. The function of SIRT6 was further investigated by over- expressing or knocking down the gene using lentiviral plasmids. To elucidate the underlying molecular mechanisms, we employed RNA sequencing, performed bioinformatics analyses, and conducted chromatin immunoprecipitation assays. Results: RNA sequencing and Western blot analyses revealed a significant reduction in SIRT6 expression in mice with cisplatin-induced acute kidney injury (AKI). Enhancing SIRT6 expression improved renal function, reduced ferroptosis, and mitigated kidney damage, whereas SIRT6 knockout exacerbated kidney injury and heightened ferroptosis. Mechanistically, RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assays demonstrated that SIRT6 inhibits ferroptosis by reducing the acetylation of histone H4K9ac at the bap1 promoter. Furthermore, in vitro studies demonstrated that the SIRT6 agonist UBCS039 can alleviate cisplatininduced acute kidney injury, highlighting its potential therapeutic role in mitigating cisplatin's

关键词： Cisplatin-induced AKI SIRT6 Ferroptosis Cisplatin bap1

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m6A Demethylase FTO-Mediated Upregulation of bap1 Induces Neuronal Ferroptosis via the p53/SLC7A11 Axis in the MPP⁺/MPTP-Induced Parkinson's Disease Model

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ACS CHEMICAL NEUROSCIENCE 2025年第3期16卷 405-416页

作者： Li, Zhengyu Chen, Xin Xiang, Wenwen Tang, Ting Gan, Li Nanchang Univ Affiliated Hosp 2 Jiangxi Med Coll Dept Neurol Nanchang 330006 Jiangxi Peoples R China

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the involvement of ferroptosis in its pathological mechanism. In this study, the effects and mechanism of BRCA1-associated protein 1 (bap1) on neuronal ferroptosis in PD were evaluated. Methods: A PD mouse model was constructed by injecting mice with MPTP. Nissl staining, immunohistochemistry, immunofluorescence, and Prussian blue staining evaluated histopathology and iron distribution. The PD cell model was constructed by subjecting SK-N-SH cells to MPP+. The m6A level of bap1 was assessed by MeRIP. mRNA levels of bap1, FTO, IGF2BP1, METTL3, YTHDF2, and SLC7A11 were evaluated utilizing RT-qPCR. Protein levels of bap1, FTO, IGF2BP1, METTL3, YTHDF2, SLC7A11, and p53 were measured by Western blot. Cell viability was assessed using CCK-8 assay, and TUNEL was used for assessing apoptosis. The levels of MDA, GSH, SOD, and Fe2+ were also measured. The interactions among molecules were verified using RIP assay, dual luciferase reporter assay, and ChIP assay. Results: SK-N-SH cells treated with MPP+ showed a decrease in overall m6A levels of bap1. FTO facilitated m6A demethylation of bap1, leading to an increased level of expression of bap1. m6A-binding protein, YTHDF2 recognized and decayed methylated mRNA of bap1, leading to the reduced bap1 stability. The FTO/bap1 axis promoted MPP+-induced ferroptosis by suppressing SLC7A11. bap1, in collaboration with p53, reduced the level of expression of SLC7A11. Knocking down bap1 mitigated ferroptosis in an MPTP mouse model. Conclusion: m6A-mediated modification of bap1 regulates neuronal ferroptosis by cooperating with p53 to decrease the level of SLC7A11. Thus, bap1 may be a potential therapeutic target for PD treatment.

关键词： bap1 FTO neuronal ferroptosis p53 Parkinson'sdisease YTHDF2

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LN-439A, a novel bap1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5

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ACTA PHARMACOLOGICA SINICA 2025年第3期46卷 715-727页

作者： Wang, Tian-tian Zhang, Long-long Li, Fu-bing Zhang, Jie Zhang, Zhi-bi Mi, Da-zhao Sun, Jian Zhang, Hong-yan Wang, Chun-yan Chen, Yi-hua Chen, Ce-shi Univ Sci & Technol China Sch Life Sci Hefei 230027 Peoples R China Chinese Acad Sci Kunming Inst Zool Chinese Acad Sci & Yunnan Prov Key Lab Anim Models & Human Dis Mech Kunming 650201 Peoples R China Kunming Med Univ Acad Biomed Engn Kunming 650500 Peoples R China East China Normal Univ Inst Biomed Sci Shanghai Frontiers Sci Ctr Genome Editing & Cell T Shanghai Key Lab Regulatory Biol Shanghai 200241 Peoples R China East China Normal Univ Sch Life Sci Shanghai 200241 Peoples R China Kunming Med Univ Affiliated Hosp 3 Kunming 650118 Peoples R China Kunming Univ Sci & Technol Fac Life Sci & Technol Kunming 650500 Peoples R China Kunming Med Univ Affiliated Hosp 1 Dept Pathol Kunming 650032 Peoples R China Kunming Med Univ Sch Pharmaceut Sci Kunming 650500 Peoples R China Kunming Med Univ Yunnan Key Lab Pharmacol Nat Prod Kunming 650500 Peoples R China Kunming Med Univ Yunnan Coll Modern Biomed Ind Kunming 650500 Peoples R China

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Kr & uuml;ppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (bap1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the bap1-KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-beta-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of bap1 by binding to the catalytic pocket of bap1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the bap1-KLF5 axis.

关键词： BLBC LN-439A KLF5 bap1 deubiquitination

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bap1-mediated ubiquitination inhibition and CAS6/AXL signaling activation in bladder cancer progression

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CYTOTECHNOLOGY 2025年第3期77卷 1-14页

作者： Chen, Liang Liu, Zhenjun Taian Publ Hlth Med Ctr Dept Special Inspect 336 Wanguan StChangcheng Rd West Tai An 271000 Shandong Peoples R China Feicheng Peoples Hosp Dept Urol Surg Tai An Peoples R China

This study investigates the role of BRCA1-associated protein 1 (bap1) in regulating the ubiquitination of SP1, YAP, and PD-L1, as well as its impact on the CAS6/AXL signaling pathway in bladder cancer progression. Transcriptomic analysis was performed using the GSE3167 dataset to identify key gene expression patterns and regulatory mechanisms. A bladder cancer mouse model was established with control (NC), OE-bap1, and KD-bap1 groups to assess the effects of bap1 overexpression and knockdown. Western blot analysis evaluated the expression levels of bap1, SP1, YAP, PD-L1, CAS6, AXL, and related signaling proteins. Functional assays, including scratch, Transwell, and colony formation, were conducted to assess cell migratory, invasive, and proliferative capacities. Additional groups included bap1, SP1 inhibitor, bap1 + SP1 inhibitor, SP1 + anti-PD-L1 monoclonal antibody, and bap1 + SP1 + anti-PD-L1 combination to evaluate the interplay of these regulatory mechanisms. bap1 overexpression significantly increased the expression of SP1, YAP, PD-L1, CAS6, AXL, and downstream signaling proteins (PI3K, STAT3, ERK 1/2, MMP-2, and MMP-9), while bap1 knockdown reduced their levels. Functional assays showed that the bap1 group exhibited significantly enhanced migratory, invasive, and proliferative abilities compared to controls. Inhibiting SP1 or combining SP1 inhibition with anti-PD-L1 treatment effectively reduced migration, invasion, and proliferation, particularly after 48 h. bap1 promotes bladder cancer progression by inhibiting the ubiquitination of SP1, YAP, and PD-L1 and activating the CAS6/AXL signaling pathway. These findings highlight bap1 as a potential therapeutic target for bladder cancer treatment.

关键词： bap1 SP1 Ubiquitination CAS6 Bladder cancer

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Bayesian analysis of the rate of spontaneous malignant mesothelioma among bap1 mutant mice in the absence of asbestos exposure

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SCIENTIFIC REPORTS 2025年第1期15卷 1-9页

作者： Nielsen, Dahlia M. Hsu, Mei Zapata III, Michael Ciavarra, Giovanni van Zyl, Leonel North Carolina State Univ Dept Biol Sci Raleigh NC 27695 USA ArrayXpress Inc Raleigh NC USA Luman Clin & Regulatory Morristown NJ USA

Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline bap1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.

关键词： Mesothelioma Asbestos bap1 Mouse studies Historical control data Bayesian statistics

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VCP Promotes Cholangiocarcinoma Development by Mediating bap1 Ubiquitination-Dependent Degradation

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Cancer Science 2025年第0期 2025 Mar 23页

作者： Zhang, Peiying Liu, Xiangning Liu, Yue Zhu, Hongdao Zheng, Churun Ling, Qi Yan, Fangjie He, Qiaojun Zhu, Hong Yuan, Tao Yang, Bo Institute of Pharmacology & Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University Hangzhou China The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China Innovation Institute for Artificial Intelligence in Medicine Zhejiang University Hangzhou China The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China School of Medicine Hangzhou City University Zhejiang Hangzhou China

Cholangiocarcinoma (CCA), recognized for its high malignancy, has been an enormous challenge due to lacking effective treatment therapy over the past decades. Recently, the targeted therapies, such as Pemigatinib and Ivosidenib, have provided new treatment options for patients carrying fibroblast growth factor receptor (FGFR) and isocitrate dehydrogenase 1/2 (IDH1/2) mutations, but only ~30% of patients harbor these mutants;it is urgent to explore novel targets and therapeutic therapies. The frequent downregulation of bap1 has been observed in CCA, and the low expression of bap1 is closely related to the poor prognosis of CCA. However, there are no effective interventions to re-activate bap1 protein;blocking its degradation may provide a feasible strategy for bap1-downregulation CCA treatment. In this study, we demonstrated the tumor-suppressive roles of bap1 in CCA and identified VCP functions as the key upstream regulator mediated by bap1 protein homeostasis. Mechanistically, VCP binds to bap1 and promotes the latter's ubiquitination degradation via the ubiquitin-proteasome pathway, thus promoting cell proliferation and inhibiting cell apoptosis. Moreover, we found that VCP inhibitors inhibited CCA cell growth and promoted cell apoptosis by blocking bap1 ubiquitination degradation. Collectively, our findings not only provided a novel mechanism underlying the aberrant low expression of bap1 in CCA but also verified the anti-tumor effect of VCP inhibitors in CCA, offering a novel therapeutic target for CCA treatment. © 2025 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

关键词： bap1 cell apoptosis cholangiocarcinoma ubiquitination VCP

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VHL、PBRM1、bap1、SETD2 基因在肾透明细胞癌中的表达及临床意义

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中华腔镜泌尿外科杂志（电子版） 2025年第2期19卷 198-204页

作者：曾丽华林碧云蔡敏仪易智君王晓冰陆元志 524000 湛江，广东医科大学附属医院病理诊断研究中心 516000 广东，惠州市中心人民医院病理科 524000 湛江，广东医科大学附属医院临床生物样本库 510000 广州，暨南大学第一附属医院病理科

目的探讨VHL、PBRM1、bap1、SETD2 基因在肾透明细胞癌（ccRCC）组织中的表达水平及临床意义。方法收集惠州市中心人民医院2016 年1 月1 日至2021 年12 月31 日手术切除的ccRCC 组织，采用免疫组织化学法检测VHL、PBRM1、bap1、SETD2 ... 详细信息

目的探讨VHL、PBRM1、bap1、SETD2 基因在肾透明细胞癌（ccRCC）组织中的表达水平及临床意义。方法收集惠州市中心人民医院2016 年1 月1 日至2021 年12 月31 日手术切除的ccRCC 组织，采用免疫组织化学法检测VHL、PBRM1、bap1、SETD2 基因在104 例原发ccRCC 组织及癌旁正常肾小管组织的表达水平，利用统计软件分析基因表达与临床病理特征、预后的相关性。结果VHL、PBRM1、bap1、SETD2 在ccRCC 组织中表达阳性率分别为51.92%、85.58%、60.58%和60.58%，而在正常肾小管组织中的阳性率分别为89.42%、98.08%、98.08%和99.04%，ccRCC 的阳性率显著低于癌旁正常肾小管组织（P＜0.001）。进一步发现bap1 和SETD2 阴性表达与肿瘤最大径＞4 cm 及TNM 分期Ⅲ～Ⅳ期相关（P＜0.05），其中bap1 阴性表达还与脉管浸润相关（P=0.001）。VHL 基因表达缺失在未出血坏死的肿瘤中占比高（P=0.009）。Kaplan -Meier 分析显示ccRCC 患者无复发生存期与bap1 阴性表达呈负相关（P=0.023）。相关性分析显示，VHL 与bap1、SETD2 表达存在相关性（r=0.470 及0.269，均P＜0.05）;SETD2 与PBRM1 和bap1 表达存在相关性（r=0.244 及0.357，均P＜0.05）。结论VHL、PBRM1、bap1、SETD2 在ccRCC 中存在表达缺失，并且不同基因表达之间存在相关性。bap1 与SETD2 阴性表达与ccRCC 的肿瘤较大、分期高和侵袭转移有关，提示它们是潜在预后不良因素。bap1 阴性表达与ccRCC 患者不良预后有关，无复发生存期更短，可能是ccRCC 新的潜在预后标记。

关键词：肾透明细胞癌肿瘤分子生物学 VHL PBRM1 bap1 SETD2

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The bap1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer

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JOURNAL OF BIOLOGICAL CHEMISTRY 2015年第48期290卷 28643-28663页

作者： Daou, Salima Hammond-Martel, Ian Mashtalir, Nazar Barbour, Haithem Gagnon, Jessica Iannantuono, Nicholas V. G. Nkwe, Nadine Sen Motorina, Alena Pak, Helen Yu, Helen Wurtele, Hugo Milot, Eric Mallette, Frederick A. Carbone, Michele Affar, El Bachir Univ Montreal Maisonneuve Rosemont Hosp Res Ctr Montreal PQ H3C 3J7 Canada Univ Montreal Dept Med Montreal PQ H3C 3J7 Canada Univ Hawaii Canc Ctr Thorac Oncol Program Honolulu HI 96813 USA

The deubiquitinase (DUB) and tumor suppressor bap1 catalyzes ubiquitin removal from histone H2A Lys-119 and coordinates cell proliferation, but how bap1 partners modulate its function remains poorly understood. Here, we report that bap1 forms two mutually exclusive complexes with the transcriptional regulators ASXL1 and ASXL2, which are necessary for maintaining proper protein levels of this DUB. Conversely, bap1 is essential for maintaining ASXL2, but not ASXL1, protein stability. Notably, cancer-associated loss of bap1 expression results in ASXL2 destabilization and hence loss of its function. ASXL1 and ASXL2 use their ASXM domains to interact with the C-terminal domain (CTD) of bap1, and these interactions are required for ubiquitin binding and H2A deubiquitination. The deubiquitination-promoting effect of ASXM requires intramolecular interactions between catalytic and non-catalytic domains of bap1, which generate a composite ubiquitin-binding interface (CUBI). Notably, the CUBI engages multiple interactions with ubiquitin involving (i) the ubiquitin carboxyl hydrolase catalytic domain of bap1, which interacts with the hydrophobic patch of ubiquitin, and (ii) the CTD domain, which interacts with a charged patch of ubiquitin. Significantly, we identified cancer-associated mutations of bap1 that disrupt the CUBI and notably an in-frame deletion in the CTD that inhibits its interaction with ASXL1/2 and DUB activity and deregulates cell proliferation. Moreover, we demonstrated that bap1 interaction with ASXL2 regulates cell senescence and that ASXL2 cancer-associated mutations disrupt bap1 DUB activity. Thus, inactivation of the bap1/ASXL2 axis might contribute to cancer development.

关键词： cancer biology cell proliferation cellular senescence deubiquitylation (deubiquitination) epigenetics ASXL bap1 Calypso histone H2A ubiquitination Polycomb Group Proteins

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