title: DEPDC1B coordinates de-adhesion events and cell-cycle progression at mitosis.
abstract: Cells entering mitosis become rounded, lose attachment to the substrate, and increase their cortical rigidity. Pivotal to these events is the dismantling of focal adhesions (FAs). How mitotic reshaping is linked to commitment to divide is unclear. Here, we show that DEPDC1B, a protein that accumulates in G2, coordinates de-adhesion events and cell-cycle progression at mitosis. DEPDC1B functions as an inhibitor of a RhoA-based signaling complex, which assembles on the FA-associated protein tyrosine phosphatase, receptor type, F (PTPRF) and mediates the integrity of FAs. By competing with RhoA for the interaction with PTPRF, DEPDC1B promotes the dismantling of FAs, which is necessary for the morphological changes preceding mitosis. The circuitry is relevant in whole organisms, as shown by the control exerted by the DEPDC1B/RhoA/PTPRF axis on mitotic dynamics during zebrafish development. Our results uncover an adhesion-dependent signaling mechanism that coordinates adhesion events with the control of cell-cycle progression.
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy; Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marchesi
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montani
authors.affiliation: Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Deflorian
authors.affiliation: Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: D'Antuono
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cuomo
authors.affiliation: Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bologna
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS, Centro di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture (PZ), Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Mazzoccoli
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonaldi
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy; Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy; Dipartimento di Scienze della Salute, Università degli Studi di Milano, 20142 Milan, Italy. Electronic address: pierpaolo.difiore@ieo.eu.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.affiliation: Istituto Europeo di Oncologia (IEO), 20141 Milan, Italy; Fondazione IFOM-Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy. Electronic address: francesco.nicassio@iit.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicassio
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C000595201:DEPDC1B protein, zebrafish; D029961:Zebrafish Proteins