Identification of a Novel E2F3 Product Suggests a Mechanism for Determining Specificity of Repression by Rb Proteins

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2000 Apr 25

PMID 10779352

Citations 91

Authors

G Leone

F Nuckolls

S Ishida

M Adams

R Sears

L Jakoi

A Miron

J R Nevins

Affiliations

Soon will be listed here.

Abstract

The tumor suppressor function of Rb is intimately related to its ability to interact with E2F and repress the transcription of E2F target genes. Here we describe a novel E2F product that specifically interacts with Rb in quiescent cells. This novel E2F, which we term E2F3b, is encoded by a unique mRNA transcribed from an intronic promoter within the E2F3 locus. The E2F3b RNA differs from the previously characterized E2F3 RNA, which we now term E2F3a, by the utilization of a unique coding exon. In contrast to the E2F3a product that is tightly regulated by cell growth, the E2F3b product is expressed equivalently in quiescent and proliferating cells. But, unlike the E2F4 and E2F5 proteins, which are also expressed in quiescent cells and form complexes with the p130 protein, the E2F3b protein associates with Rb and represents the predominant E2F-Rb complex in quiescent cells. Thus, the previously described specificity of Rb function as a transcriptional repressor in quiescent cells coincides with the association of Rb with this novel E2F product.

Citing Articles

E2F3a activates Gadd45b gene expression through PPARα-mediated transcriptional regulation in hepatic cells.

Woo M, Khalil A, Gonzalez F, Kim J Mol Cells. 2024; 47(12):100148.

PMID: 39537030 PMC: 11647606. DOI: 10.1016/j.mocell.2024.100148.

The E2F family: a ray of dawn in cardiomyopathy.

Wei J, Gao C, Lu C, Wang L, Dong D, Sun M Mol Cell Biochem. 2024; 480(2):825-839.

PMID: 38985251 DOI: 10.1007/s11010-024-05063-4.

Expanding Roles of the E2F-RB-p53 Pathway in Tumor Suppression.

Zhou Y, Nakajima R, Shirasawa M, Fikriyanti M, Zhao L, Iwanaga R Biology (Basel). 2023; 12(12).

PMID: 38132337 PMC: 10740672. DOI: 10.3390/biology12121511.

The role of alternative pre-mRNA splicing in cancer progression.

Choi S, Cho N, Kim E, Kim K Cancer Cell Int. 2023; 23(1):249.

PMID: 37875914 PMC: 10594706. DOI: 10.1186/s12935-023-03094-3.

Roles of E2F family members in the diagnosis and prognosis of head and neck squamous cell carcinoma.

Li Y, Huang Y, Li B, Yang K BMC Med Genomics. 2023; 16(1):38.

PMID: 36855110 PMC: 9976507. DOI: 10.1186/s12920-023-01470-6.

References

HERRERA R, Sah V, Williams B, Makela T, Weinberg R, Jacks T . Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts. Mol Cell Biol. 1996; 16(5):2402-7. PMC: 231229. DOI: 10.1128/MCB.16.5.2402. View

DeGregori J, Kowalik T, Nevins J . Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. Mol Cell Biol. 1995; 15(8):4215-24. PMC: 230660. DOI: 10.1128/MCB.15.8.4215. View

Sears R, Ohtani K, Nevins J . Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol Cell Biol. 1997; 17(9):5227-35. PMC: 232373. DOI: 10.1128/MCB.17.9.5227. View

Nevins J . Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ. 1998; 9(8):585-93. View

La Thangue N . DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control. Trends Biochem Sci. 1994; 19(3):108-14. DOI: 10.1016/0968-0004(94)90202-x. View

Smith E, Leone G, DeGregori J, Jakoi L, Nevins J . The accumulation of an E2F-p130 transcriptional repressor distinguishes a G0 cell state from a G1 cell state. Mol Cell Biol. 1996; 16(12):6965-76. PMC: 231700. DOI: 10.1128/MCB.16.12.6965. View

Hurford Jr R, Cobrinik D, Lee M, Dyson N . pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev. 1997; 11(11):1447-63. DOI: 10.1101/gad.11.11.1447. View

Sherr C . Mammalian G1 cyclins. Cell. 1993; 73(6):1059-65. DOI: 10.1016/0092-8674(93)90636-5. View

Dynlacht B, Moberg K, Lees J, Harlow E, Zhu L . Specific regulation of E2F family members by cyclin-dependent kinases. Mol Cell Biol. 1997; 17(7):3867-75. PMC: 232239. DOI: 10.1128/MCB.17.7.3867. View

10.

Ikeda M, Jakoi L, Nevins J . A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation. Proc Natl Acad Sci U S A. 1996; 93(8):3215-20. PMC: 39585. DOI: 10.1073/pnas.93.8.3215. View

11.

Krek W, Xu G, Livingston D . Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell. 1995; 83(7):1149-58. DOI: 10.1016/0092-8674(95)90141-8. View

12.

Helin K, Ed H . The retinoblastoma protein as a transcriptional repressor. Trends Cell Biol. 1993; 3(2):43-6. DOI: 10.1016/0962-8924(93)90150-y. View

13.

Hunter T, Pines J . Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994; 79(4):573-82. DOI: 10.1016/0092-8674(94)90543-6. View

14.

Krek W, Ewen M, Shirodkar S, Arany Z, Kaelin Jr W, Livingston D . Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase. Cell. 1994; 78(1):161-72. DOI: 10.1016/0092-8674(94)90582-7. View

15.

Marti A, Wirbelauer C, Scheffner M, Krek W . Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. Nat Cell Biol. 1999; 1(1):14-9. DOI: 10.1038/8984. View

16.

Qin X, Livingston D, Kaelin Jr W, Adams P . Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc Natl Acad Sci U S A. 1994; 91(23):10918-22. PMC: 45137. DOI: 10.1073/pnas.91.23.10918. View

17.

Nevins J . E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science. 1992; 258(5081):424-9. DOI: 10.1126/science.1411535. View

18.

Sherr C, Roberts J . Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995; 9(10):1149-63. DOI: 10.1101/gad.9.10.1149. View

19.

Neuman E, Flemington E, Sellers W, Kaelin Jr W . Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol. 1994; 14(10):6607-15. PMC: 359190. DOI: 10.1128/mcb.14.10.6607-6615.1994. View

20.

Hsiao K, McMahon S, Farnham P . Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994; 8(13):1526-37. DOI: 10.1101/gad.8.13.1526. View