Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration

Journal article


Roesley, Siti Nur Ain, Suryadinata, Randy, Morrish, Emma, Tan, Anthonius Ricardo, Issa, Samah M. A., Oakhill, Jon, Bernard, Ora, Welch, Danny R. and Sarcevic, Boris. (2016). Cyclin-dependent kinase-mediated phosphorylation of breast cancer metastasis suppressor 1 (BRMS1) affects cell migration. Cell Cycle. 15(1), pp. 137 - 151. https://doi.org/10.1080/15384101.2015.1121328
AuthorsRoesley, Siti Nur Ain, Suryadinata, Randy, Morrish, Emma, Tan, Anthonius Ricardo, Issa, Samah M. A., Oakhill, Jon, Bernard, Ora, Welch, Danny R. and Sarcevic, Boris
Abstract

Expression of Breast Cancer Metastasis Suppressor 1 (BRMS1) reduces the incidence of metastasis in many human cancers, without affecting tumorigenesis. BRMS1 carries out this function through several mechanisms, including regulation of gene expression by binding to the mSin3/histone deacetylase (HDAC) transcriptional repressor complex. In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). Although CDKs are known to regulate cell cycle progression, the mutation of BRMS1 on serine 237 did not affect cell cycle progression and proliferation of MDA-MB-231 breast cancer cells; however, their migration was affected. Phosphorylation of BRMS1 does not affect its association with the mSin3/HDAC transcriptional repressor complex or its transcriptional repressor activity. The serine 237 phosphorylation site is immediately proximal to a C-terminal nuclear localization sequence that plays an important role in BRMS1-mediated metastasis suppression but phosphorylation does not control BRMS1 subcellular localization. Our studies demonstrate that CDK-mediated phosphorylation of BRMS1 regulates the migration of tumor cells.

KeywordsBRMS1; CDK; metastasis suppressor; migration
Year2016
JournalCell Cycle
Journal citation15 (1), pp. 137 - 151
PublisherTaylor & Francis
ISSN1551-4005
Digital Object Identifier (DOI)https://doi.org/10.1080/15384101.2015.1121328
Scopus EID2-s2.0-84983035811
Page range137 - 151
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited States of America
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