DEPDC1B Coordinates De-adhesion Events and Cell-Cycle Progression at Mitosis

Marchesi, Stefano; Montani, Francesca; Deflorian, Gianluca; D’Antuono, Rocco; Cuomo, Alessandro; Bologna, Serena; Mazzoccoli, Carmela; Bonaldi, Tiziana; Fiore, Pier Paolo Di; Nicassio, Francesco

doi:10.1016/j.devcel.2014.09.009

Cited by 80 publications

(106 citation statements)

References 50 publications

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“…The ARFGAP and RHOGAP domain-containing CNT-D1 (also called ARAP2; Table 1) lacks RHOGAP activity and acts as an ARF6 GAP (99). DEP1 and DEP2 coordinate cell cycle progression and interfere with RHOA and signaling despite lacking RHOGAP activity (100). OCRL1 has been shown to interact with GTP-bound RAC1 without the stimulation of its hydrolysis (101).…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins

Amin

Jaiswal

Derewenda

et al. 2016

Journal of Biological Chemistry

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RHO GTPase-activating proteins (RHOGAPs) are one of the major classes of regulators of the RHO-related protein family that are crucial in many cellular processes, motility, contractility, growth, differentiation, and development. Using database searches, we extracted 66 distinct human RHOGAPs, from which 57 have a common catalytic domain capable of terminating RHO protein signaling by stimulating the slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity of the majority of the members of RHOGAP family is largely uncharacterized. Here, we comprehensively investigated the sequence-structurefunction relationship between RHOGAPs and RHO proteins by combining our in vitro data with in silico data. The activity of 14 representatives of the RHOGAP family toward 12 RHO family proteins was determined in real time. We identified and structurally verified hot spots in the interface between RHOGAPs and RHO proteins as critical determinants for binding and catalysis. We have found that the RHOGAP domain itself is nonselective and in some cases rather inefficient under cell-free conditions. Thus, we propose that other domains of RHOGAPs confer substrate specificity and fine-tune their catalytic efficiency in cells.

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Section: Discussionmentioning

confidence: 99%

Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins

Amin

Jaiswal

Derewenda

et al. 2016

Journal of Biological Chemistry

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“…This loss of integrinbased adhesions is sufficient to cause cells in culture to adopt a nearspherical shape -the minimum energy conformation for a cell with high cortical tension (as the sphere has the least surface area for a given vol ume). At a molecular level, this rapid change in adhesion is probably triggered by activation of CDK1-cyclin B [19][20][21][22] . Although CDK1-cyclin B directly phosphorylates sev eral adhesion complex components 23 , including integ rins 24 , focal adhesion kinase and paxillin 25 Figure 1 | Cell shape changes during mitosis.…”

Section: Entry Into Mitosismentioning

confidence: 99%

Coupling changes in cell shape to chromosome segregation

Ramkumar

Baum

2016

Nat Rev Mol Cell Biol

124

132

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Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell-substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance.

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“…In addition, recent study has demonstrated that the GAP domain of DEPDC1B does not have GAP activity toward RHOA [34]. Nonetheless, it has been shown that the conserved arginine residue in the GAP domain is not required for the binding of GAP domains to Rho GTPase proteins [35].…”

Section: Resultsmentioning

confidence: 99%

Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2

Zhu

Jimenez-Cowell

et al. 2015

Experimental Cell Research

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Pitx2 is a bicoid-related homeobox transcription factor implicated in regulating left-right patterning and organogenesis. However, only a limited number of Pitx2 downstream target genes have been identified and characterized. Here we demonstrate that Pitx2 is a transcriptional repressor of DEP domain containing 1B (DEPDC1B). The first intron of the human and mouse DEP domain containing 1B genes contains multiple consensus DNA-binding sites for Pitx2. Chromatin immunoprecipitation assays revealed that Pitx2, along with histone deacetylase 1, was recruited to the first intron of Depdc1b. In contrast, RNAi-mediated depletion of Pitx2 not only enhanced the acetylation of histone H4 in the first intron of Depdc1b, but also increased the protein level of Depdc1b. Luciferase reporter assays also showed that Pitx2 could repress the transcriptional activity mediated by the first intron of human DEPDC1B. The GAP domain of DEPDC1B interacted with nucleotide-bound forms of RAC1 in vitro. In addition, exogenous expression of DEPDC1B suppressed RAC1 activation and interfered with actin polymerization induced by the guanine nucleotide exchange factor TRIO. Moreover, DEPDC1B interacted with various signaling molecules such as U2af2, Erh, and Salm. We propose that Pitx2-mediated repression of Depdc1b expression contributes to the regulation of multiple molecular pathways, such as Rho GTPase signaling.

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DEPDC1B Coordinates De-adhesion Events and Cell-Cycle Progression at Mitosis

Cited by 80 publications

References 50 publications

Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins

Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins

Coupling changes in cell shape to chromosome segregation

Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2

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