Structural highlights
Function
[TFDP1_HUMAN] Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (PubMed:20176812).[1] [RBL1_HUMAN] Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with adenovirus E1A and with SV40 large T antigen. May bind and modulate functionally certain cellular proteins with which T and E1A compete for pocket binding. May act as a tumor suppressor. [E2F5_HUMAN] Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation. May mediate growth factor-initiated signal transduction. It is likely involved in the early responses of resting cells to growth factor stimulation. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.[UniProtKB:Q6DE14]
Publication Abstract from PubMed
The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD-CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein-E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.
Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family.,Liban TJ, Medina EM, Tripathi S, Sengupta S, Henry RW, Buchler NE, Rubin SM Proc Natl Acad Sci U S A. 2017 Apr 24. pii: 201619170. doi:, 10.1073/pnas.1619170114. PMID:28439018[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zaragoza K, Begay V, Schuetz A, Heinemann U, Leutz A. Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes. Mol Cell Biol. 2010 May;30(9):2293-304. doi: 10.1128/MCB.01619-09. Epub 2010 Feb , 22. PMID:20176812 doi:http://dx.doi.org/10.1128/MCB.01619-09
- ↑ Liban TJ, Medina EM, Tripathi S, Sengupta S, Henry RW, Buchler NE, Rubin SM. Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family. Proc Natl Acad Sci U S A. 2017 Apr 24. pii: 201619170. doi:, 10.1073/pnas.1619170114. PMID:28439018 doi:http://dx.doi.org/10.1073/pnas.1619170114
