miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression
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| Creator |
Bhattacharjya, S
Nath, S Ghose, J Maiti, GP Biswas, N Bandyopadhyay, Santu Panda, CK Bhattacharyya, NP Roychoudhury, Susanta |
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| Subject |
Infectious Diseases and Immunology
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| Description |
The spindle assembly checkpoint (SAC) is a ‘wait-anaphase’ mechanism that has evolved in eukaryotic cells in response to the
stochastic nature of chromosome–spindle attachments. In the recent past, different aspects of the SAC regulation have been
described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is
repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 – which functions to inhibit anaphase entry till the
chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of
Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated
chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely
correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased
expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an
optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b
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| Publisher |
Nature Publishing Group
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| Date |
2013
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1894/1/CELL_DEATH_AND_DIFFERENTIATION__20__(_3)__430%2D442_;2013[63].pdf
Bhattacharjya, S and Nath, S and Ghose, J and Maiti, GP and Biswas, N and Bandyopadhyay, Santu and Panda, CK and Bhattacharyya, NP and Roychoudhury, Susanta (2013) miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression. Cell Death and Differentiation, 20 (3). pp. 430-442. |
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| Relation |
http://dx.doi.org/10.1038/cdd.2012.135
http://www.eprints.iicb.res.in/1894/ |
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