SUMOylation of KLF4 acts as a switch in transcriptional programs that control VSMC proliferation
SUMOylation of KLF4 acts as a switch in transcriptional programs that control VSMC proliferation
复制标题
KLF4 的 SUMO 化充当控制 VSMC 增殖的转录程序中的开关
DOI：
10.1016/j.yexcr.2016.03.001
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发表时间：
2016-03-01
影响因子：
3.7
通讯作者：
Wen, Jin-kun
中科院分区：
文献类型：
--
作者：
Nie, Chan-juan;Li, Yong Hui;Wen, Jin-kun
血管平滑肌细胞（VSMC）增殖的调节是一个重要的问题，因为它对预防病理性血管疾病有重要意义。本研究的目的是评估小泛素样修饰物（SUMO）化Kruppel样转录因子4（KLF 4）在培养细胞和球囊损伤动物模型中对VSMC增殖的调节作用。我们发现，在基础条件下，非SUMO化KLF 4与p300的结合激活了p21（p21（WAF 1/CIP 1））转录，导致VSMC生长停滞。PDGF-BB促进Ubc 9和KLF 4之间的相互作用以及KLF 4的SUMO化，这反过来又将转录辅阻遏物募集到p21启动子。p21蛋白表达减少可促进VSMC增殖。此外，SUMO化的KLF 4不影响KLF 4的表达，从而形成促进细胞增殖的正反馈环。这些结果表明，SUMO化的KLF 4通过逆转PDGF-BB诱导的KLF 4对p21的反式激活作用在细胞增殖中起重要作用。(C)2016 Elsevier Inc. All rights reserved.
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 Kruppel-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. (C) 2016 Elsevier Inc. All rights reserved.