Mol. Cell. Biol., 01 1995, 338-344, Vol 15, No. 1
Copyright © 1995, American Society for Microbiology

The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2

EJ Smith and JR Nevins
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.

The interaction of the retinoblastoma susceptibility gene product (Rb)- related p107 protein with the E2F transcription factor in S-phase cells facilitates the formation of a multicomponent complex also containing cyclin A and the p33cdk2 kinase. We have created a series of p107 mutants to assess the ability of p107 to inhibit E2F function and the role of the cyclin A/cdk2 complex in this process. We find that p107 mutants that do not bind to E2F also fail to repress E2F-dependent transcription. Moreover, we find that the ability of p107 to suppress E2F-dependent transcription is not dependent on the ability of p107 to associate with cyclin A/cdk2. Finally, an analysis of the ability of the p107 mutant proteins to suppress cell growth suggests that both E2F- dependent and E2F-independent events correlate with this activity.

This article has been cited by other articles:

• Rodier, G., Makris, C., Coulombe, P., Scime, A., Nakayama, K., Nakayama, K. I., Meloche, S. (2005). p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. J. Cell Biol. 168: 55-66 [Abstract] [Full Text]  
• Hauser, P., Ma, L., Agrawal, D., Haura, E., Cress, W. D., Pledger, W. J. (2004). Efficient Down-Regulation of Cyclin A-Associated Activity and Expression in Suspended Primary Keratinocytes Requires p21Cip1. Mol Cancer Res 2: 96-104 [Abstract] [Full Text]  
• Zhang, Z., Huong, S.-M., Wang, X., Huang, D. Y., Huang, E.-S. (2003). Interactions between Human Cytomegalovirus IE1-72 and Cellular p107: Functional Domains and Mechanisms of Up-Regulation of Cyclin E/cdk2 Kinase Activity. J. Virol. 77: 12660-12670 [Abstract] [Full Text]  
• Farkas, T., Hansen, K., Holm, K., Lukas, J., Bartek, J. (2002). Distinct Phosphorylation Events Regulate p130- and p107-mediated Repression of E2F-4. J. Biol. Chem. 277: 26741-26752 [Abstract] [Full Text]  
• Amanullah, A., Hoffman, B., Liebermann, D. A. (2000). Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15INK4B and p16INK4A. Blood 96: 475-482 [Abstract] [Full Text]  
• Gill, R. M., Hamel, P. A. (2000). Subcellular Compartmentalization of E2F Family Members Is Required for Maintenance of the Postmitotic State in Terminally Differentiated Muscle. J. Cell Biol. 148: 1187-1202 [Abstract] [Full Text]  
• Schang, L. M., Rosenberg, A., Schaffer, P. A. (2000). Roscovitine, a Specific Inhibitor of Cellular Cyclin-Dependent Kinases, Inhibits Herpes Simplex Virus DNA Synthesis in the Presence of Viral Early Proteins. J. Virol. 74: 2107-2120 [Abstract] [Full Text]  
• Meloni, A. R., Smith, E. J., Nevins, J. R. (1999). A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor. Proc. Natl. Acad. Sci. USA 96: 9574-9579 [Abstract] [Full Text]  
• Castaño, E., Kleyner, Y., Dynlacht, B. D. (1998). Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor. Mol. Cell. Biol. 18: 5380-5391 [Abstract] [Full Text]  
• Deleu, L., Fuks, F., Spitkovsky, D., Hörlein, R., Faisst, S., Rommelaere, J. (1998). Opposite Transcriptional Effects of Cyclic AMP-Responsive Elements in Confluent or p27KIP-Overexpressing Cells versus Serum-Starved or Growing Cells. Mol. Cell. Biol. 18: 409-419 [Abstract] [Full Text]  
• Fan, G., Merritt, S. E., Kortenjann, M., Shaw, P. E., Holzman, L. B. (1996). Dual Leucine Zipper-bearing Kinase (DLK) Activates p46SAPK and p38mapk but Not ERK2. J. Biol. Chem. 271: 24788-24793 [Abstract] [Full Text]  
• Duronio, R J, Brook, A, Dyson, N, O'Farrell, P H (1996). E2F-induced S phase requires cyclin E.. Genes Dev. 10: 2505-2513 [Abstract]  
• Cobrinik, D, Lee, M H, Hannon, G, Mulligan, G, Bronson, R T, Dyson, N, Harlow, E, Beach, D, Weinberg, R A, Jacks, T (1996). Shared role of the pRB-related p130 and p107 proteins in limb development.. Genes Dev. 10: 1633-1644 [Abstract]  
• Magae, J, Wu, C., Illenye, S, Harlow, E, Heintz, N. (1996). Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members. J. Cell Sci. 109: 1717-1726 [Abstract]  
• Zhu, L, Harlow, E, Dynlacht, B D (1995). p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F.. Genes Dev. 9: 1740-1752 [Abstract]