58-kDa Microspherule Protein (MSP58) Is Novel Brahma-related Gene 1 (BRG1)-associated Protein That Modulates p53/p21 Senescence Pathway

Hsu, Che Chia; Lee, Yi Chao; Yeh, Shiu Hwa; Chen, Chang Han; Wu, Chih Ching; Wang, Tsui Ying; Chen, Yu Nong; Hung, Liang‐Yi; Liu, Yaowen; Chen, Han Ku; Hsiao, Yi Ting; Wang, Wei Sheng; Tsou, Jen Hui; Tsou, Yi Huan; Wu, Mei Hsiang; Chang, Wen Chang; Deng, Lin

doi:10.1074/jbc.m111.335331

Cited by 33 publications

(32 citation statements)

References 57 publications

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“…We reasoned that this might be, at least in part, due to the changes of Msp58 protein level, since Msp58 has been shown to affect cell cycle progression through its known effects on cyclin gene expression [8, 9]. To explore this hypothesis, we used propidium iodide labeling and flow cytometry to examine cell cycle phases in WI-38 cell cultures treated with siRNAs to EDD, to Msp58, or to both partner proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Msp58 has been implicated in regulating the expression of several cyclins [8, 9, 28]. As significant changes in cell cycle progression were observed in Msp58- or EDD-depleted cells, we therefore examined whether the levels of cyclins were affected.…”

Section: Resultsmentioning

confidence: 99%

“…Msp58 may have additional roles in cell cycle regulation through its transcriptional effects on the cyclin genes [8]. Interestingly, a recent study indicates that ectopic expression of Msp58 affects the protein levels of important regulators of cell cycle, including cyclins, and has distinctive effects in cell proliferation in a cell context-dependent manner [9]. …”

Section: Introductionmentioning

confidence: 99%

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The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression

Benavides¹,

Chow-Tsang²,

Zhang³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression

Benavides¹,

Chow-Tsang²,

Zhang³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…However, it participates in other processes, including cellular senescence (Hsu et al, 2012), cell division, and survival by interacting with the centrosomal protein Statistical analysis was performed using one-way ANOVA test followed by the Benferroni method (M). Errors bars represent ± SD (n = minimum of ten cells).…”

Section: Discussionmentioning

confidence: 99%

MCRS1 Binds and Couples Rheb to Amino Acid-Dependent mTORC1 Activation

2015

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Ras homolog enriched in brain (Rheb) is critical for mechanistic target of rapamycin complex 1 (mTORC1) activation in response to growth factors and amino acids (AAs). Whereas growth factors inhibit the tuberous sclerosis complex (TSC1-TSC2), a negative Rheb regulator, the role of AAs in Rheb activation remains unknown. Here, we identify microspherule protein 1 (MCRS1) as the essential link between Rheb and mTORC1 activation. MCRS1, in an AA-dependent manner, maintains Rheb at lysosome surfaces, connecting Rheb to mTORC1. MCRS1 suppression in human cancer cells using small interference RNA or mouse embryonic fibroblasts using an inducible-Cre/Lox system reduces mTORC1 activity. MCRS1 depletion promotes Rheb/TSC2 interaction, rendering Rheb inactive and delocalizing it from lysosomes to recycling endocytic vesicles, leading to mTORC1 inactivation. These findings have important implications for signaling mechanisms in various pathologies, including diabetes mellitus and cancer.

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“…[15,25] Besides, some BRG1-associated proteins such as 58-kDa microspherule protein is also in the position to regulate the p53 pathway. [26] In this study, p53 mRNA and protein levels were elevated by BRG1 overexpression, suggesting the promotive modulation by BRG1. Consistently, the expression of MDM2, which is an antagonist of p53 impeding p53-induced apoptosis as reported before, [27,28] was suppressed by BRG1, further suggesting the promotive effects of BRG1 on p53.…”

Section: Discussionmentioning

confidence: 50%

Brahma-related gene 1 induces apoptosis in a p53-dependent manner in human rheumatoid fibroblast-like synoviocyte MH7A

Hongli

Xing²,

Li³

2016

Medicine

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Blocked apoptosis and aggressive inflammatory responses occur in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) patients. Although Brahma-related gene 1 (BRG1) is considered as a tumor suppressor, few research covers its role in RA. This study aims to reveal effects and potential mechanisms of BRG1 in human FLS cell line MH7A.BRG1 expression in MH7A cells was altered by transfection of overexpression vectors or short hairpin RNAs (shRNAs). Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry after transfection. Factors involved in inflammation and apoptosis were quantified by qPCR and Western blot. The interaction between BRG1 and p53 was assessed by immunoprecipitation (IP).Results showed that BRG1 overexpression significantly suppressed MH7A cell viability and induced apoptosis (P < 0.01), and its knockdown had opposite effects. BRG1 reduced mRNA levels of matrix metallopeptidase 3, TIMP metallopeptidase inhibitor 2, cyclooxygenase 2, and interleukin 6, implying its suppressive effects on inflammation. BRG1 interacted with and promoted p53 (P < 0.05). B-cell chronic lymphocytic leukemia/lymphoma 2 was suppressed (P < 0.05), while cytochrome c, caspase 3 (CASP3) and CASP9 were activated (P < 0.01) by BRG1. However, the regulation on these factors was abrogated by p53 knockdown (P < 0.01).These findings suggest that BRG1 may induce apoptosis and suppress inflammation in MH7A cells. Potential functional mechanisms involve the regulation of apoptotic factors by BRG1, which may depend on the recruitment and promotion of p53. This study provides the essential proof for applying BRG1 to the molecular therapy of RA.

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58-kDa Microspherule Protein (MSP58) Is Novel Brahma-related Gene 1 (BRG1)-associated Protein That Modulates p53/p21 Senescence Pathway

Cited by 33 publications

References 57 publications

The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression

The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression

MCRS1 Binds and Couples Rheb to Amino Acid-Dependent mTORC1 Activation

Brahma-related gene 1 induces apoptosis in a p53-dependent manner in human rheumatoid fibroblast-like synoviocyte MH7A

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