Abstract
E2F transcription factors regulate genes involved in cell-cycle progression. In mammalian cells, physiological E2F exists as an E2F/DP heterodimer. Currently, eight E2F and two DP subunits have been characterized. We report here the characterization of a new member of the DP family, DP-4. While DP-4 exhibits certain similarities with members of the DP family, it also possesses a number of significant differences. Thus, DP-4 forms a heterodimer with E2F subunits, binds to the E2F site and associates with pocket proteins including pRb. In contrast to DP-1, however, DP-4/E2F-1 complexes exhibit reduced DNA binding activity. Furthermore, DP-4 interferes with E2F-1-dependent transcription and delays cell-cycle progression. These results highlight an emerging complexity in the DP family of E2F subunits, and suggest that DP-4 may endow E2F heterodimers with distinct transcription properties.
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References
Allen KE, de la Luna S, Kerkhoven RM, Bernards R, La Thangue NB . (1997). J Cell Sci 110: 2819–2831.
Bandara LR, Lam EWF, Sorensen TS, Zamanian M, Girling R, La Thangue NB . (1994). EMBO J 13: 3104–3114.
de la Luna S, Allen KE, Mason SL, La Thangue NB . (1999). EMBO J 18: 212–228.
de la Luna S, Burden MJ, Lee C-W, La Thangue NB . (1996). J Cell Sci 109: 2443–2452.
Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin Jr WG, Livingston DM et al. (1996). Cell 85: 549–561.
Frolov MV, Dyson NJ . (2004). J Cell Sci 117: 2173–2181.
Girling R, Partridge JF, Bandara LR, Burden N, Totty NF, Hsuan JJ et al. (1993). Nature 362: 83–87.
Khon MJ, Leung S, Criniti V, Agromayor M, Yamasaki L . (2004). Mol Cell Biol 24: 7197–7205.
Kohn MJ, Bronson RT, Harlow E, Dyson NJ, Yamasaki L . (2003). Development 130: 1295–1305.
Krek W, Ewen ME, Shirodker S, Arany Z, Kaelin WF, Livingston DM . (1994). Cell 78: 161–172.
Logan N, Delavaine L, Graham A, Reilly C, Wilson J, Brummelkamp TR et al. (2004). Oncogene 23: 5138–5150.
Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y . (2002). Science 296: 1132–1136.
Ormondroyd E, de la Luna S, La Thangue NB . (1995). Oncogene 11: 1437–1446.
Rogers KT, Higgins PDR, Milla MM, Phillips RS, Horowitz JM . (1996). Proc Natl Acad Sci USA 93: 7594–7599.
Stevens C, La Thangue NB . (2003). Arch Biochem Biophys 412: 157–169.
Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L, Jacks T . (1998). Mol Cell 2: 293–304.
Yamasaki L, Bronson R, Williams BO, Dyson N, Harlow E, Jacks T . (1998). Nat Genet 18: 360–364.
Zhang Y, Chellappan SP . (1995). Oncogene 10: 2085–2093.
Zheng N, Fraenkel E, Pabo CO, Pavletich NP . (1999). Genes Dev 13: 666–674.
Zhu W, Giangrande PH, Nevins JR . (2004). EMBO J 23: 4615–4626.
Acknowledgements
We thank Rosemary Williams for help in preparing the manuscript, and the AICR, EC, MRC and CRUK for supporting the work.
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Milton, A., Luoto, K., Ingram, L. et al. A functionally distinct member of the DP family of E2F subunits. Oncogene 25, 3212–3218 (2006). https://doi.org/10.1038/sj.onc.1209343
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DOI: https://doi.org/10.1038/sj.onc.1209343
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