SUMOylation of KLF4 acts as a switch in transcriptional programs that control VSMC proliferation

详细信息    查看全文

• 作者：Chan-juan Nie^a ; Yong hui Li^a ; ^b ; Xin-hua Zhang^a ; Zhi-peng Wang^a ; Wen Jiang^a ; Yu Zhang^a ; Wei-na Yin^a ; Yong Zhang^c ; Hui-jing Shi^a ; Yan Liu^a ; Cui-ying Zheng^a ; Jing Zhang^a ; Guo-liang Zhang^d ; Bin Zheng^a ; ^{doublezb@hebmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Jin-kun Wen^a ; ^{wjk@hebmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ATRA ; All-Trans Retinoic Acid ; cdk2 ; Cyclin-Dependent Kinase 2 ; HASMC ; Human Aortic Smooth Muscle Cells ; HDAC2 ; Histone Deacetylase 2 ; KLF ; Krü ; ppel-like Factor ; LSD1 ; Lysine-Specific Demethylase 1 ; NCoR ; Nuclear Receptor Co-Repressor ; p21 ; P21WAF1/Cip1 ; PDGF ; Platelet-Derived Growth Factor ; qRT-PCR ; Quantitative Real-Time Polymerase Chain Reaction ; SRF ; Serum Response Factor ; SUMO ; Small Ubiquitin-like Modifier ; Ubc9 ; E2-Conjugating Enzyme Ubc9 ; VSMCs ; Vascular Smooth Muscle Cells
• 刊名：Experimental Cell Research
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：342
• 期：1
• 页码：20-31
• 全文大小：4896 K

文摘

The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue due to its major implications for the prevention of pathological vascular conditions. The objective of this work was to assess the function of small ubiquitin-like modifier (SUMO)ylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in cultured cells and in animal models with balloon injury. We found that under basal conditions, binding of non-SUMOylated KLF4 to p300 activated p21 (p21^WAF1/CIP1)transcription, leading to VSMC growth arrest. PDGF-BB promoted the interaction between Ubc9 and KLF4 and the SUMOylation of KLF4, which in turn recruited transcriptional corepressors to the p21 promoter. The reduction in p21 enhanced VSMC proliferation. Additionally, the SUMOylated KLF4 did not affect the expression of KLF4, thereby forming a positive feedback loop enhancing cell proliferation. These results demonstrated that SUMOylated KLF4 plays an important role in cell proliferation by reversing the transactivation action of KLF4 on p21 induced with PDGF-BB.