58-kDa microspherule protein (MSP58) is novel Brahma-related gene 1 (BRG1)-associated protein that modulates p53/p21 senescence pathway.

The Journal of Biological Chemistry
Che-Chia HsuDing-Yen Lin

Abstract

The nucleolar 58-kDa microspherule protein (MSP58) protein is a candidate oncogene implicated in modulating cellular proliferation and malignant transformation. In this study, we show that knocking down MSP58 expression caused aneuploidy and led to apoptosis, whereas ectopic expression of MSP58 regulated cell proliferation in a context-dependent manner. Specifically, ectopic expression of MSP58 in normal human IMR90 and Hs68 diploid fibroblasts, the H184B5F5/M10 mammary epithelial cell line, HT1080 fibrosarcoma cells, primary mouse embryonic fibroblasts, and immortalized NIH3T3 fibroblasts resulted in induction of premature senescence, an enlarged and flattened cellular morphology, and increased senescence-associated β-galactosidase activity. MSP58-driven senescence was strictly dependent on the presence of functional p53 as revealed by the fact that normal cells with p53 knockdown by specific shRNA or cells with a mutated or functionally impaired p53 pathway were effective in bypassing MSP58-induced senescence. At least two senescence mechanisms are induced by MSP58. First, MSP58 activates the DNA damage response and p53/p21 signaling pathways. Second, MSP58, p53, and the SWI/SNF chromatin-remodeling subunit Brahma-related gen...Continue Reading

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Citations

Mar 31, 2015·Developmental Cell·Mohamad-Ali FawalNabil Djouder
Oct 16, 2015·Journal of Experimental & Clinical Cancer Research : CR·Minxia LiuYi Cao
Aug 18, 2016·Biochemical and Biophysical Research Communications·Chuan-Pin YangDing-Yen Lin
Feb 10, 2017·Cell Death & Disease·Guihua WangJunbo Hu
Dec 19, 2018·Journal of Cardiovascular Development and Disease·Xiaojun ZhuJing-Wei Xiong
Feb 21, 2019·Molecular Biology of the Cell·Hongdan YangJungseog Kang
Jul 22, 2018·Nature Reviews. Urology·Aguirre A de Cubas, W Kimryn Rathmell
Jul 26, 2016·Experimental and Therapeutic Medicine·Chenguang LiYanfang Jiang
Feb 23, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Pan TanHai-Qin Wang

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Datasets Mentioned

BETA
BCN962

Methods Mentioned

BETA
PCR
Antibody
Transfection
flow cytometry
Immunoprecipitation
Two-hybrid
dot-blot
ChIP

Software Mentioned

Sigmascan
GraphPad
GraphPad Prism

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