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

Journal Article · Tue Mar 01 04:00:00 EST 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.03.001· OSTI ID:22746417

Nie, Chan-juan ^[1]; Li, Yong hui ^[1]; Zhang, Xin-hua; Wang, Zhi-peng; Jiang, Wen; Zhang, Yu; Yin, Wei-na ^[1]; Zhang, Yong ^[2]; Shi, Hui-jing; Liu, Yan; Zheng, Cui-ying; Zhang, Jing ^[1]; Zhang, Guo-liang ^[3]; Zheng, Bin ^[1]; Wen, Jin-kun ^[1]

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1. Department of Biochemistry and Molecular Biology, Hebei Medical University, Zhongshan East Road, Shijiazhuang 050017 (China)
2. Department of Urinary Surgery, Second Hospital of Hebei Medical University, Pingan Road, Shijiazhuang 050000 (China)
3. Third Hospital of Shijiazhuang, Shijiazhuang 050000 (China)

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{sup 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.

• OSTI ID: 22746417
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 342; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
CELL CULTURES
CELL PROLIFERATION
CHAIN REACTIONS
FEEDBACK
FUNCTIONS
GENE RECOMBINATION
GROWTH FACTORS
HISTONES
INJURIES
INTERACTIONS
LYSINE
MONOCLINIC LATTICES
MUSCLES
PHOSPHORUS 21
PHOSPHOTRANSFERASES
PLANT GROWTH
POLYMERASE CHAIN REACTION
POLYMERASES
RECEPTORS
RETINOIC ACID
SWITCHES
TRANSCRIPTION
TRANSCRIPTION FACTORS