title: RGS19 stimulates cell proliferation by deregulating cell cycle control and enhancing Akt signaling.
abstract: RGS19 is a regulator of G protein signaling which is upregulated in ovarian cancers and its overexpression promotes cell proliferation in several mammalian cell types. Here we showed that cyclin D1/3 and Cdk6 were upregulated in HEK293 cells overexpressing RGS19, while INK4A and INK4B were reduced. Moreover, RGS19 augmented serum-stimulated PTEN/PDK/Akt and Rb phosphorylations in 293/RGS19 and Caco2/RGS19 cells. These changes were reversed upon the knockdown of RGS19. Consistent with an elevated Akt activity, increased levels of phosphorylated Bad and c-Raf and a diminished expression of TSC2 were detected, thus demonstrating that RGS19 can deregulate cell proliferation via multiple pathways.
authors.affiliation: Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Prudence H
authors.initials: PH
authors.lastname: Tso
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Yung
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D002453:Cell Cycle; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D056743:Cyclin D3 / Q000096:biosynthesis / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020710:RGS Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
chemical_list: C494819:BAD protein, human; C493966:CDKN2B protein, human; D056743:Cyclin D3; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020710:RGS Proteins; D034741:RNA, Small Interfering; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D051025:bcl-Associated Death Protein; C097187:regulator of G-protein signalling 19; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human