郑晓峰 教授
RNA与蛋白质功能研究组
北京大学生命科学学院教授，博士生导师
电话：
E-mail：xiaofengz@pku.edu.cn
1、蛋白质翻译后修饰在DNA损伤应答、NF-κB、p53等信号通路中的调控作用
2、肿瘤发生发展重要调控蛋白的作用机制
3、外泌体蛋白在肿瘤转移中的作用和机制
着重开展与人类疾病相关蛋白质的功能研究。利用生物化学、分子生物学、细胞生物学、免疫学和结构生物学等技术方法，研究HSCARG 和hCINAP等蛋白在炎症和肿瘤发生发展中的调节作用、参与的信号通路及分子机制。我们的研究表明HSCARG和hCINAP分别通过影响NF-κB和p53信号通路中重要节点蛋白的泛素化和NEDD化修饰在这些通路中发挥重要的调控作用。HSCARG还参与调控抗病毒固有免疫信号通路，它通过抑制TRAF3的泛素化负调控RIG-I信号通路，最终降低干扰素的生成。此外，HSCARG通过抑制PRC1复合体的E3连接酶活性而调控H2A泛素化水平，通过影响DNA损伤修复后的恢复来影响细胞周期，揭示了H2A泛素化调控细胞周期的新机制。在hCINAP功能的研究中还证明它在核糖体18S rRNA的剪切中的重要作用，并证明hCINAP通过调控肿瘤（干）细胞的代谢影响肿瘤的增殖、耐药和转移。在类泛素化底物的研究中，识别了组蛋白H2A等新的NEDDylation修饰底物蛋白，并探讨它们在DNA损伤应答等重要生理过程中的调控作用和机制。首次证明H2A和PCNA能够发生NEDD化修饰，明确了H2A泛素化和NEDD化修饰之间的关系，并阐明了NEDD化修饰调控DNA损伤修复的分子机理。此外，我们还在鉴定影响肿瘤发展和转移的外泌体蛋白，揭示其在肿瘤转移和恶化中的作用机制。
Liao LM, Yang P, Zhang WL, Yu SY, Jing HM, Zheng XF. (2024) CD98hc promotes drug resistance in extranodal natural killer/T cell lymphoma through tumor cell-derived small extracellular vesicles. Sci. Signal., 17: eadf9388.
Zhang J, Chen YT, Gong X, Yang YF, Gu Y, Huang L, Fu JF, Zhao ML, Huang YH, Li LL, Liu WZ, Wan YJ, He XL, Ma ZF, Zhao WY, Zhang M, Tang T, Wang YZ, Thiery JP, Zheng XF, Chen LM. (2024) GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in patients with breast cancer. J. Biol. Chem., 300: 107780.
Fu JF, Zhou SR, Xu HL, Liao LM, Shen H, Du P, Zheng XF. (2023) ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucl. Acids Res., 51: 7376-7391.
Wei M, Huang XP, Liao LM, Tian YL, Zheng XF. (2023) SENP1 decreases RNF168 phase separation to promote DNA damage repair and drug resistance in colon cancer. Cancer Res., 83: 2908-2923.
Zhuge RP, Huang XP, Zheng XF. (2023) Insight into the multi-faceted roles of the structure and function of an atypical adenylate kinase AK6/hCINAP. Prog. Biochem. Biophys., 50: 1122- 1132.
Huang XP, Zhao Y, Wei M, Zhuge RP, Zheng XF. (2023) hCINAP alleviates senescence by regulating MDM2 via p14ARF and the HDAC1/CoREST complex. J. Mol. Cell Biol., 15: mjad015.
Zhuge RQ, Wang C, Wang J, Yu SY, Liao LM, Zheng XF. (2023) hCINAP controls lineage differentiation of embryonic stem cells by regulating NEDD4 liquid-liquid phase separation-mediated YAP1 activation. Cell Rep., 42: 111935.
Liao LM, Xu HL, Zhao YH, Zheng XF. (2023) Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies. Front. Med., 17: 805-822.
Zhao Y, Huang XP, Zhu D, Wei M, Luo JC, Yu SY, Tian YL, Zheng XF. (2022) Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy. Cell Death Differ., 29: 2531-2544.
Huang XP, Yang YF, Zhu D, Zhao Y, Wei M, Li K, Zhu HH, Zheng XF. (2022) PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3by stabilizing oncoprotein PML-RAR alpha. Cell. Mol. Life Sci., 79: 319.
Yu SY, Zang WC, Qiu YC, Liao LM, Zheng XF. (2022) Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene, 41: 46-56.
Zhu D, Xu RD, Huang XP, Tang ZF, Tian YL, Zhang JF, Zheng XF. (2021) Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1.Cell. Death. Differ., 28: 1773-1789.
Xu RD, Yang YF, Zheng XF. (2021) Unique structural features of the adenylate kinase hCINAP/AK6 and its multifaceted functions in carcinogenesis and tumor progression. FEBS Lett., 595: 2071-2084.
Chen SW, Wang YB, Liao LM, Meng L, Li JJ, Shi C, Han H,Zheng XF, Shen H. (2020) Similar repair effects of human placenta, bone marrow mesenchymal stem cells and their exosomes for damaged SVOG ovarian granulosa cells. Stem. Cell. Int., 8861557.
Yang YF, Yang CZ, Li TT, Yu SY, Gan TT, Hu JZ, Cui J, Zheng XF. (2020) The deubiquitinase usp38 promotes nhej repair through regulation of HDAC1 activity and regulates cancer cell response to genotoxic insults. Cancer Res., 80: 719-731.
Zang WC, Zheng XF. (2020) Structure and functions of cellular redox sensor HSCARG/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer.Free Radic Biol Med., 160: 768-774.
Chen SW, Wang YB, Liao LM, Meng L, Li JJ, Shi C, Han H, Zheng XF, Shen H. (2020) Similar repair effects of human placenta, bone marrow mesenchymal stem cells and their exosomes for damaged SVOG ovarian granulosa cells. Stem. Cell. Int., 8861557.
卫敏、王洁、付剑锋、王超、周思汝、李钰琳、徐慧琳、赵瑜涵、祝东岳、施予欣
