报告题目：Epigenetic and post-translational regulations of hypoxia-mediated gene transcription and epithelial-mesenchymal transition.
报 告 人： Kou-Juey Wu， Director, Research Center for Tumor Medical Science
Chair Professor，Grad. Institute of Cancer Biology，China Medical Univ.
主 持 人: 李国红研究员
时 间：2016.03.18 AM 10:00
地 点：中国科学院生物物理研究所9408会议室
报告摘要：
Mammalian cells cope with hypoxic stress through stabilization of hypoxia-inducible factors (HIFs). Hypoxia/HIF-1a induces epithelial-mesenchymal transition through regulating specific histone modifications1-3. HIF-1a stability is regulated at the post-translational levels through ubiquitination. The HIF-1a-specific deubiquitinase has not been identified. Here we show that HAUSP (USP7) deubiquitinase interacts with and deubiquitinates HIF-1a to increase its stability and functions. Hypoxia further induces K63-linked polyubiquitination of HAUSP to enhance its functions. Knockdown of HAUSP decreases global H3K56 acetylation levels. K63-polyubiquitinated HAUSP is crucial for HIF-1a-induced gene transcription and stabilization of the HIF-1a-CBP complex to maintain the H3K56Ac levels. A structural model is presented to illustrate the mechanism. Quantitative chromatin immunoprecipitation (qChIP) assays showed the corresponding histone mark changes in the promoters of HIF-1a target genes. ChIP-seq analysis of HAUSP and HIF-1a binding reveals two motifs responsive to hypoxia. These results provide a novel mechanism of HAUSP-mediated HIF-1a stabilization and HIF-1a target gene transcription.
迎感兴趣的老师、同学积极参加。
报 告 人： Kou-Juey Wu， Director, Research Center for Tumor Medical Science
Chair Professor，Grad. Institute of Cancer Biology，China Medical Univ.
主 持 人: 李国红研究员
时 间：2016.03.18 AM 10:00
地 点：中国科学院生物物理研究所9408会议室
报告摘要：
Mammalian cells cope with hypoxic stress through stabilization of hypoxia-inducible factors (HIFs). Hypoxia/HIF-1a induces epithelial-mesenchymal transition through regulating specific histone modifications1-3. HIF-1a stability is regulated at the post-translational levels through ubiquitination. The HIF-1a-specific deubiquitinase has not been identified. Here we show that HAUSP (USP7) deubiquitinase interacts with and deubiquitinates HIF-1a to increase its stability and functions. Hypoxia further induces K63-linked polyubiquitination of HAUSP to enhance its functions. Knockdown of HAUSP decreases global H3K56 acetylation levels. K63-polyubiquitinated HAUSP is crucial for HIF-1a-induced gene transcription and stabilization of the HIF-1a-CBP complex to maintain the H3K56Ac levels. A structural model is presented to illustrate the mechanism. Quantitative chromatin immunoprecipitation (qChIP) assays showed the corresponding histone mark changes in the promoters of HIF-1a target genes. ChIP-seq analysis of HAUSP and HIF-1a binding reveals two motifs responsive to hypoxia. These results provide a novel mechanism of HAUSP-mediated HIF-1a stabilization and HIF-1a target gene transcription.
迎感兴趣的老师、同学积极参加。