Loss of circadian protein TIMELESS accelerates the progression of cellular senescence

Xiaomeng Shen; Mingzhe Li; Zebin Mao; Wenhua Yu

doi:10.1016/j.bbrc.2018.08.040

Loss of circadian protein TIMELESS accelerates the progression of cellular senescence

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2784-2791. doi: 10.1016/j.bbrc.2018.08.040. Epub 2018 Aug 9.

Authors

Xiaomeng Shen¹, Mingzhe Li¹, Zebin Mao², Wenhua Yu³

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People's Republic of China.
² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People's Republic of China. Electronic address: zbmao@bjmu.edu.cn.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People's Republic of China. Electronic address: yuwenhua@hsc.pku.edu.cn.

PMID: 30100061
DOI: 10.1016/j.bbrc.2018.08.040

Abstract

TIMELESS protein is known to be essential for normal circadian rhythms. Aging is a deleterious process which affects all the physiological functions of complex organisms including the circadian rhythms. The circadian aging may produce disorganization among the circadian rhythms, arrhythmicity and even, disconnection from the environment, resulting in a detrimental situation to the organism. However, the role of circadian genes on the aging process is poorly understood. In present study, we found TIMELESS was down-regulated in cellular senescence, and further research indicated E2F1 bound to the promotor of TIMELESS and regulated its expression in cellular senescence. Knockdown of TIMELESS accelerated cellular senescence induced by ectopic expression of RasV12, and overexpression of TIMELESS delayed this kind onset of senescence. Meanwhile, micrococcal nuclease assays proved depletion of TIMELESS exacerbated genomic instability at the onset of senescence. Together, our data reveal that TIMELESS plays a role in OIS, which is associated with genome stability changing.

Keywords: E2F1; Senescence; TIMELESS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Proteins / antagonists & inhibitors
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Cell Line
Cellular Senescence / drug effects
Cellular Senescence / genetics*
Circadian Rhythm / genetics*
E2F1 Transcription Factor / genetics*
E2F1 Transcription Factor / metabolism
Fibroblasts / cytology
Fibroblasts / drug effects
Fibroblasts / metabolism*
Gene Expression Regulation
Genes, Reporter
Genomic Instability
HEK293 Cells
Humans
Hydrogen Peroxide / pharmacology
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / metabolism
Promoter Regions, Genetic
Protein Binding
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
beta-Galactosidase / genetics
beta-Galactosidase / metabolism
ras Proteins / genetics
ras Proteins / metabolism

Substances

Cell Cycle Proteins
E2F1 Transcription Factor
E2F1 protein, human
Intracellular Signaling Peptides and Proteins
RNA, Small Interfering
TIMELESS protein, human
Hydrogen Peroxide
beta-Galactosidase
ras Proteins