p27 Kip1 regulates the microtubule bundling activity of PRC1.

Autor: Perchey RT; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Serres MP; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Nowosad A; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Creff J; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Callot C; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Gay A; Cancer Research Center of Toulouse (CRCT), INSERM U1037, CNRS ERL5294, University of Toulouse, Toulouse, France., Manenti S; Cancer Research Center of Toulouse (CRCT), INSERM U1037, CNRS ERL5294, University of Toulouse, Toulouse, France., Margolis RL; Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA., Hatzoglou A; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France., Besson A; LBCMCP, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062 Toulouse Cedex, France. Electronic address: arnaud.besson@univ-tlse3.fr.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2018 Nov; Vol. 1865 (11 Pt A), pp. 1630-1639. Date of Electronic Publication: 2018 Aug 16.
DOI: 10.1016/j.bbamcr.2018.08.010
Abstrakt: Cytokinesis begins in anaphase with the formation of the central spindle. PRC1 is a microtubule associated protein that plays an essential role in central spindle formation by crosslinking antiparallel microtubules. We have identified PRC1 as a novel binding partner for p27 Kip1 (p27). p27 is a cyclin-CDK inhibitor that causes cell cycle arrest in G1. However, p27 has also been involved in the regulation of G2/M progression and cytokinesis, as well as of other cellular processes, including actin and microtubule cytoskeleton dynamics. We found that p27 interferes with the ability of PRC1 to bind to microtubules, without affecting PRC1 dimerization or its capacity to interact with other partners such as KIF4. In this way, p27 inhibited microtubule bundling by PRC1 in vitro and prevented the extensive microtubule bundling phenotype caused by PRC1 overexpression in cells in culture. Finally, co-expression of p27 or a p27 mutant that does not bind cyclin-CDKs inhibited multinucleation induced by PRC1 overexpression. Together, our results suggest that p27 may participate in the regulation of mitotic progression in a CDK-independent manner by modulating PRC1 activity.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: