Proto-oncogenic properties of the DP family of proteins
- PMID: 7731707
Proto-oncogenic properties of the DP family of proteins
Abstract
The cellular transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product, cyclins and cyclin-dependent kinases. DRTF1/E2F is a heterodimeric DNA binding activity which arises when a member of two distinct families of proteins, DP and E2F, interact as DP/E2F heterodimers, for example, DP-1 and E2F-1. In DRTF1/E2F the activity of DP-1 is under cell cycle control, possibly by phosphorylation, and in many types of cells it is a frequent, if not general DNA binding component of DRTF1/E2F. The expression of other DP proteins, such as DP-2, is tissue-restricted. Here, we show that DP-1 and DP-2 are integrated with another growth regulating pathway which involves signal transduction emanating from activated Ras protein. Thus, activated Ha-ras can co-operate with DP-1 or DP-2 in the transformation of rat embryo fibroblasts, establishing for the first time that DP proteins are endowed with proto-oncogenic activity. Moreover, an analysis of a dominant-negative and mutant DP-1 proteins suggests that the primary target through which DP-1 mediates its oncogenic activity is unlikely to be due to the regulation of E2F site-transcription, suggesting an E2F-independent effector function for DP-1. These results therefore establish DP genes as proto-oncogenes and thus argue that deregulating the normal control of DP protein activity will be important in promoting aberrant cellular proliferation.
Similar articles
-
A new member of the DP family, DP-3, with distinct protein products suggests a regulatory role for alternative splicing in the cell cycle transcription factor DRTF1/E2F.Oncogene. 1995 Oct 19;11(8):1437-46. Oncogene. 1995. PMID: 7478568
-
Integration of a growth-suppressing BTB/POZ domain protein with the DP component of the E2F transcription factor.EMBO J. 1999 Jan 4;18(1):212-28. doi: 10.1093/emboj/18.1.212. EMBO J. 1999. PMID: 9878064 Free PMC article.
-
Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1.Oncogene. 1999 Jan 21;18(3):593-605. doi: 10.1038/sj.onc.1202345. Oncogene. 1999. PMID: 9989809
-
Transcriptional control by E2F.Semin Cancer Biol. 1995 Apr;6(2):99-108. doi: 10.1006/scbi.1995.0013. Semin Cancer Biol. 1995. PMID: 7647312 Review.
-
DP and E2F proteins: coordinating transcription with cell cycle progression.Curr Opin Cell Biol. 1994 Dec;6(6):859-66. doi: 10.1016/0955-0674(94)90057-4. Curr Opin Cell Biol. 1994. PMID: 7880534 Review.
Cited by
-
Functional interaction between DP-1 and p53.Mol Cell Biol. 1996 Oct;16(10):5888-95. doi: 10.1128/MCB.16.10.5888. Mol Cell Biol. 1996. PMID: 8816502 Free PMC article.
-
Molecular cloning and expression pattern of the DP members of the chicken E2F transcription factor.Gene Expr. 1997;6(5):259-73. Gene Expr. 1997. PMID: 9368098 Free PMC article.
-
Inhibition of E2F-mediated transcription by p202.EMBO J. 1996 Oct 15;15(20):5668-78. EMBO J. 1996. PMID: 8896460 Free PMC article.
-
ACGH detects distinct genomic alterations of primary intrahepatic cholangiocarcinomas and matched lymph node metastases and identifies a poor prognosis subclass.Sci Rep. 2018 Jul 13;8(1):10637. doi: 10.1038/s41598-018-28941-6. Sci Rep. 2018. PMID: 30006612 Free PMC article.
-
Adenoviral-E2F-1 radiosensitizes p53wild-type and p53null human prostate cancer cells.Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):238-46. doi: 10.1016/j.ijrobp.2005.04.033. Int J Radiat Oncol Biol Phys. 2005. PMID: 15993550 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Research Materials