| Structural highlights
Function
LIN9_HUMAN Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition.[1] [2]
Publication Abstract from PubMed
Genes encoding the core cell cycle machinery are transcriptionally regulated by the MuvB family of protein complexes in a cell cycle-specific manner. Complexes of MuvB with the transcription factors B-MYB and FOXM1 activate mitotic genes during cell proliferation. The mechanisms of transcriptional regulation by these complexes are still poorly characterised. Here, we combine biochemical analysis and in vitro reconstitution, with structural analysis by cryo-electron microscopy and cross-linking mass spectrometry, to functionally examine these complexes. We find that the MuvB:B-MYB complex binds and remodels nucleosomes, thereby exposing nucleosomal DNA. This remodelling activity is supported by B-MYB which directly binds the remodelled DNA. Given the remodelling activity on the nucleosome, we propose that the MuvB:B-MYB complex functions as a pioneer transcription factor complex. In this work, we rationalise prior biochemical and cellular studies and provide a molecular framework of interactions on a protein complex that is key for cell cycle regulation.
Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling.,Koliopoulos MG, Muhammad R, Roumeliotis TI, Beuron F, Choudhary JS, Alfieri C Nat Commun. 2022 Aug 29;13(1):5075. doi: 10.1038/s41467-022-32798-9. PMID:36038598[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gagrica S, Hauser S, Kolfschoten I, Osterloh L, Agami R, Gaubatz S. Inhibition of oncogenic transformation by mammalian Lin-9, a pRB-associated protein. EMBO J. 2004 Nov 24;23(23):4627-38. Epub 2004 Nov 11. PMID:15538385 doi:http://dx.doi.org/7600470
- ↑ Sandoval R, Xue J, Tian X, Barrett K, Pilkinton M, Ucker DS, Raychaudhuri P, Kineman RD, Luque RM, Baida G, Zou X, Valli VE, Cook JL, Kiyokawa H, Colamonici OR. A mutant allele of BARA/LIN-9 rescues the cdk4-/- phenotype by releasing the repression on E2F-regulated genes. Exp Cell Res. 2006 Aug 1;312(13):2465-75. Epub 2006 Apr 25. PMID:16730350 doi:http://dx.doi.org/S0014-4827(06)00156-X
- ↑ Koliopoulos MG, Muhammad R, Roumeliotis TI, Beuron F, Choudhary JS, Alfieri C. Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling. Nat Commun. 2022 Aug 29;13(1):5075. doi: 10.1038/s41467-022-32798-9. PMID:36038598 doi:http://dx.doi.org/10.1038/s41467-022-32798-9
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