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Genes Genomics. 2018 Sep 27. doi: 10.1007/s13258-018-0747-4. [Epub ahead of print]

Hip2 ubiquitin-conjugating enzyme has a role in UV-induced G1/S arrest and re-entry.

Author information

1
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul, 02841, Republic of Korea.
2
Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.
3
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul, 02841, Republic of Korea. skang@korea.ac.kr.

Abstract

Regulation of cell cycle arrest and re-entry triggered by DNA damage is vital for cell division and growth and is also involved in cell survival. UV radiation can generate lesions in the DNA, which results in cell cycle arrest and the induction of the DNA repair process. However, the mechanism of promoting cell cycle progression following DNA repair is elusive. The primary aim of this study is to investigate whether Hip2 ubiquitin-conjugating enzyme has a role in UV-induced G1/S arrest and re-entry. The phase of HEK293 cells was synchronized at the G1/S border using thymidine. The synchronously proliferating cells were exposed to UV radiation to cause DNA damage. We investigated the expression of p53, Hip2, p21, cyclin D and E proteins that are involved in the cell cycle progression. Finally, we examined changes in the phosphorylation of Hip2 after UV radiation treatment using the pIMAGO™ assay. When cells were exposed to UV radiation, expression of p53 was elevated, and the cell cycle was arrested at the G1/S boundary. In response to the increased p53 level, Hip2 became phosphorylated and activated through the inhibition of its degradation. The phosphorylated Hip2 inhibited p53, thereby suppressing the expression of p21, a downstream signal, and sequentially stimulating cyclin D and cyclin E to induce re-entry to the cell cycle. Our studies demonstrate that Hip2 works as a regulator in UV-induced cell cycle arrest and re-entry.

KEYWORDS:

Cell cycle; Hip2; P53; UV radiation

PMID:
30264212
DOI:
10.1007/s13258-018-0747-4

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