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      Rich1 negatively regulates the epithelial cell cycle, proliferation and adhesion by CDC42/RAC1-PAK1-Erk1/2 pathway.

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          Abstract

          Rich1, a previously identified Rho GTPase-activating protein (RhoGAP), was found to have close relationship with Rho GTPase family members in multiple cellular processes in nervous cells and platelets. But the exact role of Rich1 in epithelial cells remains obscure. The present investigation demonstrated that up-regulation of Rich1 could cause S-phase arrest, proliferation inhibition and adhesion decline with F-actin amount decrease in epithelial cells. Further exploration in hepatocyte HL7702 revealed that overexpression of Rich1 could greatly elevate the intrinsic GTPase activities on both of CDC42 and RAC1 by stimulating GTP hydrolysis, which consequently attenuated the activities of the Rho proteins and the phosphorylation level of those in PAK1-ERK1/2 signaling cascade. While the GAP domain deleted Rich1 variant or silence of endogenous Rich1 expression could not result in any of the biological effects. It is indicated that Rich1, completely different from in other types of cells, might act as a crucial upstream negative regulator via its GAP domain in control of epithelial cell cycle, proliferation and focal adhesion through CDC42/RAC1-PAK1-ERK1/2 signaling pathway and F-actin dynamics.

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          Author and article information

          Journal
          Cell. Signal.
          Cellular signalling
          Elsevier BV
          1873-3913
          0898-6568
          Sep 2015
          : 27
          : 9
          Affiliations
          [1 ] Institute of Molecular Medicine and Oncology, Chongqing Medical University, Chongqing 400016, China. Electronic address: zhangjun1017@sohu.com.
          [2 ] Institute of Molecular Medicine and Oncology, Chongqing Medical University, Chongqing 400016, China.
          [3 ] Chongqing Institute for Food and Drug Control, Chongqing 4001121, China.
          Article
          S0898-6568(15)00157-6
          10.1016/j.cellsig.2015.05.009
          26004135
          714d429d-e26b-4cc7-8dbe-e20f0d443174
          History

          S-phase arrest,CDC42,Cell proliferation,Focal adhesion,RAC1,Rich1

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