title: VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways.
abstract: Vasopressin-activated Ca2+-mobilizing (VACM)-1 gene product is a 780-amino acid membrane protein that shares sequence homology with cullins, a family of genes involved in the regulation of cell cycle. However, when expressed in vitro, VACM-1 attenuates basal and vasopressin- and forskolin-induced cAMP production. Mutating the PKA-dependent phosphorylation site in the VACM-1 sequence (S730AVACM-1) prevents this inhibitory effect. To further examine the biological role of VACM-1, we studied the effect of VACM-1 and S730AVACM-1 proteins on cellular proliferation and gene expression in Chinese hamster ovary and COS-1 cells. Cellular proliferation of VACM-1-expressing cell lines was significantly lower compared with that of the vector-transfected cells, whereas it was significantly increased in S730AVACM-1-derived cell lines. Furthermore, expression of VACM-1 but not S730AVACM-1 protein retarded cytokinesis and prevented MAPK phosphorylation. Screening with the Human PathwayFinder-1 GEArray system and subsequent Western blot analysis demonstrated that VACM-1 induces p53 mRNA and protein expression. In summary, VACM-1 inhibits cellular growth by a mechanism that involves cAMP, MAPK phosphorylation, and p53 expression.
authors.affiliation: Dept. of Biology, Peale Science Center, Hope College, Holland, MI 49422-9000, USA.
authors.forename: C
authors.initials: C
authors.lastname: Van Dort
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.forename: K
authors.initials: K
authors.lastname: Parmelee
authors.forename: B
authors.initials: B
authors.lastname: Capps
authors.forename: A
authors.initials: A
authors.lastname: Poel
authors.forename: L
authors.initials: L
authors.lastname: Listenberger
authors.forename: J
authors.initials: J
authors.lastname: Kossoris
authors.forename: B
authors.initials: B
authors.lastname: Wasilevich
authors.forename: D
authors.initials: D
authors.lastname: Murrey
authors.forename: P
authors.initials: P
authors.lastname: Clare
authors.forename: M
authors.initials: M
authors.lastname: Burnatowska-Hledin
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D016466:CHO Cells; D019556:COS Cells / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D044842:Cullin Proteins / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D044842:Cullin Proteins; D016159:Tumor Suppressor Protein p53; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases