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Int. J. Mol. Sci. 2019, 20(2), 310; https://doi.org/10.3390/ijms20020310

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

1
China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou 450008, China
2
Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
3
Department of Pharmaceutical Science & Engineering, Seowon University, Cheongju 28674, Korea
*
Author to whom correspondence should be addressed.
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)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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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