Disease relevance of Dlc1

• Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP [1].
• Expression of higher levels of tGAP1 by infection of somatic cells with recombinant adenoviruses demonstrated that tGAP1 efficiently induces apoptosis, which to our knowledge is the first such demonstration for a RhoGAP protein [2].

High impact information on Dlc1

• At its carboxy-terminal end, p190 contains a region that is conserved in the breakpoint cluster region, n-chimaerin, and Rho-GAP [3].
• Strikingly, this shift in favor of nonpyramidal morphologies is also inhibited by the expression of dominant negative mutants of Cdc42 and Rac and by RhoGAP p190 [4].
• This novel p122-RhoGAP binds to PLC-delta 1 and activates the phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolyzing activity of PLC-delta 1 [5].
• Clustering of cortactin during podosome formation causes the rapid, local dispersion of myosin and tropomyosin, and interferes with the F-actin binding of h1calponin, consistent with a RhoGAP-mediated reduction of contractility [6].
• Six cDNAs represent human homologs of genes known in other species, namely, mouse HSPE71, Rat RhoGAP protein, S cerevisiae leucyl tRNA synthetase and S cerevisiae chromosome II ORF YBLO44W [7].

Biological context of Dlc1

• A novel testicular RhoGAP-domain protein induces apoptosis [2].
• These findings define a pathway in which Fyn activity regulates the phosphorylation of p190, leading to an increase in RhoGAP activity with a subsequent increase in RhoGDP, which in turn, regulates the morphological changes that accompany oligodendrocyte differentiation [8].
• CAMGAP1 is composed of an Src homology 3 (SH3) domain, multiple WW domains, a proline-rich region, a PH domain and a RhoGAP domain, and has the domain architecture similar to ARHGAP9 and ARHGAP12 [9].

Anatomical context of Dlc1

• As Rho-GAP signaling had been shown to be influenced by p190 levels, leading to the disassembly of focal adhesion contacts and the loss of cytoskeletal architecture, we also measured the changes in Rho-GAP during prostate regression [10].
• We isolated a novel RhoGAP domain-containing tGAP1 protein from male germ cells that exhibits unusual properties [2].
• Oligophrenin-1 is a RhoGTPase-activating protein (RhoGAP) that is involved in the regulation of shape changes in dendritic spines, and outgrowth of axons and dendrites in the brain [11].

Associations of Dlc1 with chemical compounds

• Ang II-induced increase in p(190) RhoGAP tyrosine phosphorylation was attenuated by genistein [12].

Other interactions of Dlc1

• A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities [5].

Analytical, diagnostic and therapeutic context of Dlc1

• Ral-GAP also differed from Rho-GAP and Rap-GAP by virtue of its elution from a gel filtration column with proteins of Mr greater than 10(6) [13].

References