G1 cyclins control the retinoblastoma gene product growth regulation activity via upstream mechanisms - PubMed (original) (raw)
Affiliations
- PMID: 7794807
G1 cyclins control the retinoblastoma gene product growth regulation activity via upstream mechanisms
L E Horton et al. Cell Growth Differ. 1995 Apr.
Abstract
Inactivation of the retinoblastoma gene product (pRb) occurs concomitant with the appearance of its hyperphosphorylated form in mid to late G1. Multiple cyclin/CDK complexes are implicated in the cell cycle phosphorylation of pRb. Using in vivo expression systems, we show that cyclins A, E, D1, D2, and D3 each function to phosphorylate and inactivate pRb. In vivo, G1 cyclin/kinase complexes enhance the phosphorylation of pRb, and these effects of cyclin/kinases on pRb can be overcome by the addition of p21, a wide spectrum inhibitor of G1 kinases. Kinases associated with cyclins A, E, and D1 phosporylate pRb indistinguishably in vivo, according to proteolytic maps. Although cyclin D1 has been reported to bind to pRb directly, requiring the pRb-binding motif LXCXE, a mutant D1 lacking the pRb-binding motif remains able to phosphorylate pRb in vivo and in vitro and is also able to reverse the growth-inhibitory properties of pRb in intact cells. Finally, coexpression of G1 cyclins and kinases represses pRb-mediated growth inhibition in Saos-2 cells. The multiplicity of mechanisms for pRb phosphorylation and inactivation suggests that several pathways exist for the regulation of pRb by phosphorylation.
Similar articles
- Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein.
Nielsen NH, Emdin SO, Cajander J, Landberg G. Nielsen NH, et al. Oncogene. 1997 Jan 23;14(3):295-304. doi: 10.1038/sj.onc.1200833. Oncogene. 1997. PMID: 9018115 - Apoptosis induced by ectopic expression of cyclin D1 but not cyclin E.
Sofer-Levi Y, Resnitzky D. Sofer-Levi Y, et al. Oncogene. 1996 Dec 5;13(11):2431-7. Oncogene. 1996. PMID: 8957085 - Regulation of cell cycle entry and G1 progression by CSF-1.
Roussel MF. Roussel MF. Mol Reprod Dev. 1997 Jan;46(1):11-8. doi: 10.1002/(SICI)1098-2795(199701)46:1<11::AID-MRD3>3.0.CO;2-U. Mol Reprod Dev. 1997. PMID: 8981358 Review. - Cyclin D1 as a cellular proto-oncogene.
Bates S, Peters G. Bates S, et al. Semin Cancer Biol. 1995 Apr;6(2):73-82. doi: 10.1006/scbi.1995.0010. Semin Cancer Biol. 1995. PMID: 7647309 Review.
Cited by
- Expression and localization of Ski determine cell type-specific TGFbeta signaling effects on the cell cycle.
Jacob C, Grabner H, Atanasoski S, Suter U. Jacob C, et al. J Cell Biol. 2008 Aug 11;182(3):519-30. doi: 10.1083/jcb.200710161. J Cell Biol. 2008. PMID: 18695043 Free PMC article. - Docking-dependent regulation of the Rb tumor suppressor protein by Cdk4.
Wallace M, Ball KL. Wallace M, et al. Mol Cell Biol. 2004 Jun;24(12):5606-19. doi: 10.1128/MCB.24.12.5606-5619.2004. Mol Cell Biol. 2004. PMID: 15169919 Free PMC article. - Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways.
Kimura H, Nakamura T, Ogawa T, Tanaka S, Shiota K. Kimura H, et al. Nucleic Acids Res. 2003 Jun 15;31(12):3101-13. doi: 10.1093/nar/gkg406. Nucleic Acids Res. 2003. PMID: 12799438 Free PMC article. - The B-domain lysine patch of pRB is required for binding to large T antigen and release of E2F by phosphorylation.
Brown VD, Gallie BL. Brown VD, et al. Mol Cell Biol. 2002 Mar;22(5):1390-401. doi: 10.1128/MCB.22.5.1390-1401.2002. Mol Cell Biol. 2002. PMID: 11839806 Free PMC article. - Integration of the pRB and p53 cell cycle control pathways.
Stewart CL, Soria AM, Hamel PA. Stewart CL, et al. J Neurooncol. 2001 Feb;51(3):183-204. doi: 10.1023/a:1010615822317. J Neurooncol. 2001. PMID: 11407592 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Research Materials