乳腺癌细胞中PCAF/WSTF/MOF复合物调控H3K9ac和H4K16ac  

H3K9ac and H4K16ac were Regulated Through PCAF/WSTF/MOF Complex in Breast Cancer Cells

作　　者：李云翠 刘岩[2,3] 邓宇 王淑青[2,4] 宋明珠[4] 陈苏[5] 常剑锋[5] 杨之耘 

机构地区：[1]华北理工大学基础医学院,唐山063000 [2]华北理工大学生命科学学院,唐山063000 [3]唐山市肿瘤医院肿瘤防治研究所,唐山063000 [4]开滦总医院肾脏内科,唐山063000 [5]同济大学生命科学与技术学院,上海200092

出　　处：《基因组学与应用生物学》2016年第5期1008-1012,共5页Genomics and Applied Biology

基　　金：国家自然科学基金(81302324);华北理工大学大学生创新创业训练计划项目(X2015142)共同资助

摘　　要：为了研究WSTF调控Ras相关乳腺癌细胞特性的机制。研究采用Western Blot检测WSTF磷酸化和组蛋白修饰水平;经GST pull-down验证WSTF与PCAF、MOF之间的相互作用,采用乙酰化酶活性实验验证PCAF和MOF酶活性;经Ch IP、Real-time PCR检测基因表达,并采用体内成瘤实验验证细胞成瘤能力。研究发现WSTF与PCAF、MOF之间存在相互作用。Ras通路激活后,WSTF磷酸化水平上调,使其与PCAF的结合增强的同时与MOF的结合减弱。这一变化引起PCAF的乙酰化酶活性上调而MOF的酶活性下调,导致H3K9ac上调和H4K16ac下调。组蛋白修饰的变化引起通路下游肿瘤相关基因表达发生改变,增强细胞成瘤能力。综上,WSTF蛋白通过调节与PCAF和MOF的相互作用,影响下游H3K9ac和H4K16ac水平及肿瘤相关基因表达,调控乳腺癌细胞成瘤能力。In order to study WSTF（Williams syndrome transcription factor） regulation mechanism involved in Ras signal related to breast cancer cells. Western blot was used to detect WSTF phosphorylation and histone modification levels. GST pull-down was conducted to testify the interaction between WSTF, PCAF and MOF.Acetyltransferase activity of PCAF and MOF was tested via HAT activity assay. Ch IP and Real-time PCR were applied to confirm gene expression. In vivo tumor growth analysis was used to test tumor formation capability.Results revealed an interaction between WSTF, PCAF and MOF. WSTF phosphorylation increased following Ras activation with enhancement of the association between WSTF and PCAF while the association between WSTF and MOF was attenuated. The changes resulted in an increase of PCAF activity and decrease of MOF, and upregulation of H3K9 ac and downregulation of H4K16 ac followed by gene expression changes and enhancement of tumor formation. In conclusion, WSTF involved in regulation of PCAF and MOF, meanwhile, tumor formation was affected as a consequence of changes of H3K9 ac, H4K16 ac and tumor related gene expression.

关 键 词：WSTF MOF PCAF 

分 类 号：R737.9[医药卫生—肿瘤]