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Decision for cell fate: deubiquitinating enzymes in cell cycle checkpoint

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Abstract

All organs consisting of single cells are consistently maintaining homeostasis in response to stimuli such as free oxygen, DNA damage, inflammation, and microorganisms. The cell cycle of all mammalian cells is regulated by protein expression in the right phase to respond to proliferation and apoptosis signals. Post-translational modifications (PTMs) of proteins by several protein-editing enzymes are associated with cell cycle regulation by their enzymatic functions. Ubiquitination, one of the PTMs, is also strongly related to cell cycle regulation by protein degradation or signal transduction. The importance of deubiquitinating enzymes (DUBs), which have a reversible function for ubiquitination, has recently suggested that the function of DUBs is also important for determining the fate of proteins during cell cycle processing. This article reviews and summarizes the diverse roles of DUBs, including DNA damage, cell cycle processing, and regulation of histone proteins, and also suggests the possibility for therapeutic targets.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

ATR:

ATM and Rad3-related

DDR:

DNA damage response

DUB:

Deubiquitinating enzyme

UPP:

Ubiquitin proteasomal pathway

USP:

Ubiquitin-specific protease

UCH:

Ubiquitin carboxy terminal hydrolases

OTU:

Ovarian tumor domain

MJD:

Machado–Joseph disease

JAMM:

Jab1/MPN domain-associated metalloisopeptidase

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013-0141).

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  1. Department of Biomedical Science, CHA University, 335 Pangyo-Ro, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 463-400, Republic of Korea

    Key-Hwan Lim, Myoung-Hyun Song & Kwang-Hyun Baek

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Lim, KH., Song, MH. & Baek, KH. Decision for cell fate: deubiquitinating enzymes in cell cycle checkpoint. Cell. Mol. Life Sci. 73, 1439–1455 (2016). https://doi.org/10.1007/s00018-015-2129-2

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