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Open AccessArticle

p21WAF1/Cip1 Regulation by hYSK1 Activates SP-1 Transcription Factor and Increases MMP-2 Expression under Hypoxic Conditions

China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou 450008, China
Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Department of Pharmaceutical Science & Engineering, Seowon University, Cheongju 28674, Korea
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 310;
Received: 27 November 2018 / Revised: 26 December 2018 / Accepted: 11 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)
The hYSK1, a serine/threonine kinase (STK)-25, has been implicated in a variety of cellular functions including cell migration and polarity. We have recently reported that hYSK1 down-regulated the expression and functions of p16INK4a, a cell cycle regulatory protein, thereby enhancing migration and growth of cancer cells under hypoxic conditions. In this study, we further investigated the mechanisms underlying downregulation of p16INK4a and anti-migratory function of hYSK1. Our study revealed that p21WAF1/Cip1 is a novel binding partner of hYSK1. Moreover, the interaction between hYSK1 and p21WAF1/Cip1 led to the inhibition of SP-1 transcriptional activity, as revealed by a significant down-regulation of SP-1-mediated transactivation of p16INK4a promoter, and accelerated MMP-2 expression. Conversely, the knock-down of hYSK1 enhanced the p16INK4a promoter activity and protein expression, and diminished MMP-2 transcription and protein levels in hypoxic conditions as compared to control. Taken together, hYSK1 blocks the p21WAF1/Cip1 functions by direct interaction and inhibits the p16INK4a expression and induces MMP-2 expression by its regulations of SP-1 transcriptional activity under the hypoxia conditions. View Full-Text
Keywords: hYSK1; p21WAF1/Cip1; MMP-2; tumor migration; hypoxia hYSK1; p21WAF1/Cip1; MMP-2; tumor migration; hypoxia
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MDPI and ACS Style

Lee, M.-H.; Kundu, J.K.; Choi, B.Y. p21WAF1/Cip1 Regulation by hYSK1 Activates SP-1 Transcription Factor and Increases MMP-2 Expression under Hypoxic Conditions. Int. J. Mol. Sci. 2019, 20, 310.

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