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Unraveling the role of aurora A beyond centrosomes and spindle assembly: implications in muscle differentiation
Author(s) -
Dhanasekaran Karthigeyan,
Bose Arnab,
Rao Vinay J.,
Boopathi Ramachandran,
Shankar Shilpa Rani,
Rao Vinay Kumar,
Swaminathan Amrutha,
Vasudevan Madavan,
Taneja Reshma,
Kundu Tapas K.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800997
Subject(s) - centrosome , microbiology and biotechnology , mitosis , biology , aurora kinase , plk1 , phosphorylation , polo like kinase , spindle apparatus , cell cycle , genetics , gene , cell division , cell
Aurora kinases are critical mitotic serine/threonine kinases and are often implicated in tumorigenesis. Recent studies of the interphase functions for aurora kinase (Aurk)A have considerably expanded our understanding of its role beyond mitosis. To identify the unknown targets of AurkA, we used peptide array‐based screening and found E2F4 to be a novel substrate. Phosphorylation of E2F4 by AurkA at Ser75 regulates its DNA binding and subcellular localization. Because E2F4 plays an important role in skeletal muscle differentiation, we attempted to gain insight into E2F4 phosphorylation in this context. We observed that a block in E2F4 phosphorylation retained it better within the nucleus and inhibited muscle differentiation. RNA sequencing analysis revealed a perturbation of the gene network involved in the process of muscle differentiation and mitochondrial biogenesis. Collectively, our findings establish a novel role of AurkA in the process of skeletal muscle differentiation.—Dhanasekaran, K., Bose, A., Rao, V. J., Boopathi, R., Shankar, S. R., Rao, V. K., Swaminathan, A., Vasudevan, M., Taneja, R., Kundu, T. K. Unravelling the role of aurora A beyond centrosomes and spindle assembly: implications in muscle differentiation. FASEB J. 33, 219–230 (2019). www.fasebj.org