| Structural highlights
6c48 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| NonStd Res: | |
| Gene: | LIN9, BARA, TGS (HUMAN), MYBL2, BMYB (HUMAN), LIN52, C14orf46 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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] [MYBB_HUMAN] Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene.[3]
Publication Abstract from PubMed
The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation.
Structural mechanism of Myb-MuvB assembly.,Guiley KZ, Iness AN, Saini S, Tripathi S, Lipsick JS, Litovchick L, Rubin SM Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1808136115. doi:, 10.1073/pnas.1808136115. PMID:30224471[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Cervellera M, Raschella G, Santilli G, Tanno B, Ventura A, Mancini C, Sevignani C, Calabretta B, Sala A. Direct transactivation of the anti-apoptotic gene apolipoprotein J (clusterin) by B-MYB. J Biol Chem. 2000 Jul 14;275(28):21055-60. doi: 10.1074/jbc.M002055200. PMID:10770937 doi:http://dx.doi.org/10.1074/jbc.M002055200
- ↑ Guiley KZ, Iness AN, Saini S, Tripathi S, Lipsick JS, Litovchick L, Rubin SM. Structural mechanism of Myb-MuvB assembly. Proc Natl Acad Sci U S A. 2018 Sep 17. pii: 1808136115. doi:, 10.1073/pnas.1808136115. PMID:30224471 doi:http://dx.doi.org/10.1073/pnas.1808136115
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