Enhanced tumor cell growth suppression by an N-terminal truncated retinoblastoma protein
H J Xu, K Xu, Y Zhou, J Li, W F Benedict, S X Hu, H J Xu, K Xu, Y Zhou, J Li, W F Benedict, S X Hu
Abstract
The retinoblastoma (RB) gene encodes a nuclear phosphoprotein of 928 amino acids (pRB). Thus far, much effort in RB research has been focused on both the viral oncoprotein-binding domains and the C-terminal domain, whereas little is known about the N-terminal moiety of the protein. We report here that an N-terminal truncated RB protein of approximately 94 kDa (pRB94) exerts more potent cell growth suppression as compared to the full-length pRB protein in a diversity of tumor cell lines examined, including those having a normal endogenous RB gene. Tumor cells transfected with the pRB94-expressing plasmids displayed multiple morphological changes frequently associated with cellular senescence and/or apoptosis. They failed to enter S phase and rapidly died. The pRB94 expressed in recipient tumor cells had a longer half-life than the full-length pRB protein and tended to remain in an active un- or hypophosphorylated form. Since it has also been found that N-terminal truncated RB proteins often accumulated in growth-arrested and/or differentiated tumor cells, we suggest that N-terminal truncation of pRB may be one of the cellular mechanisms modulating the RB protein function in cell-cycle control.
References
- Science. 1990 Aug 24;249(4971):912-5
- Genes Chromosomes Cancer. 1994 Apr;9(4):251-60
- Cell Growth Differ. 1990 Sep;1(9):429-37
- Oncogene. 1991 Feb;6(2):317-22
- EMBO J. 1991 Apr;10(4):857-64
- Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5257-61
- Oncogene. 1991 Jul;6(7):1139-46
- Cancer Res. 1991 Aug 15;51(16):4481-5
- Cell. 1991 Oct 18;67(2):293-302
- Cancer Res. 1991 Dec 1;51(23 Pt 1):6381-4
- Genes Dev. 1992 Jun;6(6):953-64
- Cell. 1992 Jul 24;70(2):337-50
- Mol Cell Biol. 1992 Dec;12(12):5620-31
- Mol Cell Biol. 1993 Jun;13(6):3384-91
- Biochem Biophys Res Commun. 1993 May 14;192(3):1139-46
- Oncogene. 1993 Oct;8(10):2659-72
- Cell Growth Differ. 1993 Aug;4(8):629-35
- Cell. 1993 Nov 19;75(4):779-90
- Mol Cell Biol. 1994 Jan;14(1):299-309
- Proc Natl Acad Sci U S A. 1994 May 10;91(10):4165-9
- Methods Biochem Anal. 1980;26:1-45
- Science. 1984 Mar 9;223(4640):1028-33
- Cancer Res. 1985 Apr;45(4):1437-43
- Nature. 1986 Oct 16-22;323(6089):643-6
- Science. 1987 Mar 13;235(4794):1394-9
- Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831-5
- Science. 1987 Jun 26;236(4809):1657-61
- Nature. 1987 Oct 15-21;329(6140):642-5
- Science. 1988 Dec 16;242(4885):1563-6
- Oncogene. 1989 Jun;4(6):807-12
- Virology. 1989 Aug;171(2):331-41
- Science. 1989 Dec 8;246(4935):1300-3
- Science. 1990 Feb 9;247(4943):712-5
- Proc Natl Acad Sci U S A. 1990 Apr;87(7):2770-4
- Science. 1990 Aug 10;249(4969):666-9
- Oncogene. 1991 Jan;6(1):37-42
Source: PubMed