VACM-1, a cul-5 gene,inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways |
| |
Authors: | Van Dort C Zhao P Parmelee K Capps B Poel A Listenberger L Kossoris J Wasilevich B Murrey D Clare P Burnatowska-Hledin M |
| |
Affiliation: | Dept. of Biology, Peale Science Center, Hope College, Holland, MI 49422-9000, USA. |
| |
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. mitogen-activated protein kinase; cytokinesis; vasopressin-activated calcium-mobilizing receptor |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《American journal of physiology. Cell physiology》浏览原始摘要信息 |
|
点击此处可从《American journal of physiology. Cell physiology》下载全文 |
|