Zinc finger and BTB domain-containing protein 32 is encoded by the ZBTB32gene. The protein is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins,[1][2] and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.
The protein recruits histone modification enzymes to chromatin to affect gene activation.[3] ZBTB32 recruits corepressors, such as N-CoR and HDACs to its target genes, induces repressive chromatin states and acts cooperatively with other proteins, e.g. with Blimp-1,[3] to suppress the transcription of genes .[3]
It contains a N-terminal BTB/POZ domain (IPR000210) or a SKP1/BTB/POZ domain (IPR011333), and three C-terminal zinc fingers, Znf_C2H2_sf. (IPR036236), Znf_C2H2_type domain (IPR013087), a Znf_RING/FYVE/PHD domain (IPR013083), followed by a putative Znf_UBZ3 domain (REF).
Aliases for Zinc Finger and BTB Domain Containing 32 (ZBTB32) protein
Fanconi Anemia Zinc Finger Protein (FAZF),
Testis Zinc Finger Protein (TZFP),
FANCC-Interacting Protein (FAXP),
Zinc Finger Protein 538 (ZNF538),
Repressor of GATA3 (ROG)
Judged by the ability of ZBTB32 to regulate epigenetic modifications, it is reasonable to postulate the protein affects DNA damage signaling and DNA repair. In humans, histone methylation has been shown to regulate DNA mismatch repair (REF). The physical interaction of the proliferating cell nuclear antigen (PCNA) sliding clamp with the MutLα (PMS2-MLH1) endonuclease is required for mismatch repair activation (REF.) The enzyme and pathway database Reactome (REF and link) assigns to ZBTB32 a role in the recognition of DNA damage by the PCNA-containing replication complex (link R-HSA-110314; but please be aware: UAF1 is not ZBTB32 as confirmed by the database curators recently and the error is/was associated with a reference sequence update. Changes expected to be visible in the database in Dec 2017/Jan 2018) and Fanconi Anemia pathway (link R-HSA-6783310). A putative ZBTB32 RING-UBZ3 (RING-Ubiquitin-binding zinc finger domain 3; ZBTB32 zf 2 and 3) domain might interact with Ubiquitin (Ub) as other UBZ containing proteins do with Ub-PCNA (REF).
Fanconi Anemia
References
↑ 1.01.1Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. PMID10572087.
↑Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. PMID10572087.
↑Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID14499622.
↑Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I (June 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene. 22 (26): 4035–46. doi:10.1038/sj.onc.1206610. PMID12821938.
Further reading
Lin W, Lai CH, Tang CJ, Huang CJ, Tang TK (November 1999). "Identification and gene structure of a novel human PLZF-related transcription factor gene, TZFP". Biochemical and Biophysical Research Communications. 264 (3): 789–95. doi:10.1006/bbrc.1999.1594. PMID10544010.
Tsuzuki S, Enver T (May 2002). "Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein". Blood. 99 (9): 3404–10. doi:10.1182/blood.V99.9.3404. PMID11964310.
Dai MS, Chevallier N, Stone S, Heinrich MC, McConnell M, Reuter T, Broxmeyer HE, Licht JD, Lu L, Hoatlin ME (July 2002). "The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific". The Journal of Biological Chemistry. 277 (29): 26327–34. doi:10.1074/jbc.M201834200. PMID11986317.
Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I (June 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene. 22 (26): 4035–46. doi:10.1038/sj.onc.1206610. PMID12821938.
Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID14499622.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein–protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID16713569.
Ikeda R, Yoshida K, Inoue I (May 2007). "Identification of FAZF as a novel BMP2-induced transcription factor during osteoblastic differentiation". Journal of Cellular Biochemistry. 101 (1): 147–54. doi:10.1002/jcb.21165. PMID17171645.
