Structural highlights
Function
[ZBT17_HUMAN] Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The POZ/BTB domain is an evolutionarily conserved motif found in approximately 40 zinc-finger transcription factors (POZ-ZF factors). Several POZ-ZF factors are implicated in human cancer, and POZ domain interaction interfaces represent an attractive target for therapeutic intervention. Miz-1 (Myc-interacting zinc-finger protein) is a POZ-ZF factor that regulates DNA-damage-induced cell cycle arrest and plays an important role in human cancer by virtue of its interaction with the c-Myc and BCL6 oncogene products. The Miz-1 POZ domain mediates both self-association and the recruitment of non-POZ partners. POZ-ZF factors generally function as homodimers, although higher-order associations and heteromeric interactions are known to be physiologically important; crucially, the interaction interfaces in such large complexes have not been characterised. We report here the crystal structure of the Miz-1 POZ domain up to 2.1 A resolution. The tetrameric organisation of Miz-1 POZ reveals two types of interaction interface between subunits; an interface of alpha-helices resembles the dimerisation interface of reported POZ domain structures, whereas a novel beta-sheet interface directs the association of two POZ domain dimers. We show that the beta-sheet interface directs the tetramerisation of the Miz-1 POZ domain in solution and therefore represents a newly described candidate interface for the higher-order homo- and hetero-oligomerisation of POZ-ZF proteins in vivo.
A beta-sheet interaction interface directs the tetramerisation of the Miz-1 POZ domain.,Stead MA, Trinh CH, Garnett JA, Carr SB, Baron AJ, Edwards TA, Wright SC J Mol Biol. 2007 Nov 2;373(4):820-6. Epub 2007 Aug 21. PMID:17880999[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. An alternative pathway for gene regulation by Myc. EMBO J. 1997 Sep 15;16(18):5672-86. PMID:9312026 doi:10.1093/emboj/16.18.5672
- ↑ Schneider A, Peukert K, Eilers M, Hanel F. Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc. Curr Top Microbiol Immunol. 1997;224:137-46. PMID:9308237
- ↑ Basu S, Liu Q, Qiu Y, Dong F. Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1433-8. doi: 10.1073/pnas.0804863106., Epub 2009 Jan 22. PMID:19164764 doi:10.1073/pnas.0804863106
- ↑ Stead MA, Trinh CH, Garnett JA, Carr SB, Baron AJ, Edwards TA, Wright SC. A beta-sheet interaction interface directs the tetramerisation of the Miz-1 POZ domain. J Mol Biol. 2007 Nov 2;373(4):820-6. Epub 2007 Aug 21. PMID:17880999 doi:10.1016/j.jmb.2007.08.026
