Biology:Zinc finger protein 521
 Generic protein structure example |
Zinc finger protein 521 is a protein that in humans is encoded by the ZNF521 gene.[1] It was formerly named EHZF (early hematopoietic zinc finger protein), and is the human homolog of mouse EVI3/Zpf521.[2]
Function
ZNF521 is a nuclear protein and functions as a transcriptional regulator. ZNF521 has been shown to complex with SMAD1 and SMAD4, enhancing the transcriptional activity of a BMP2/4 responsive element, in response to BMP2. Further, it serves as an inhibitor of early B-cell factor (EBF1).[2]
ZNF521 has been found to play a role in erythroid cell differentiation through direct binding with GATA-1. In hematopoietic cells, ZNF521 mRNA is widely expressed in CD34+ early hematopoietic progenitors, and its expression level declines rapidly during their differentiation.
Structure
ZNF521 is a transcription factor with an N-terminal repressor motif and 30 Krüppel-like zinc finger (ZF)3 finger domains. Its N-terminal motif contains 12 amino acids, and is conserved among other ZF transcriptional repressors, including FOG-1, FOG-2, BCL11A, and SALL1.[3]
Clinical significance
ZNF521 mRNA has been detected in most cases of acute myelogenous leukemia (AML). It is expressed in several hematopoietic cell lines, such as K562 and HEL, derived from AML and CML at blast crisis.
Due to its action as a transcriptional inhibitor of EBF1, ZNF521 overexpression can lead to the inhibition of B-cell differentiation, and potential induction of B-cell malignancies. Monoallelic selection of EBF1 or PAX5, which is downstream of EBF1, has been found in B-progenitor acute lymphoblastic leukemia.[4]
Interactions
See also
References
- ↑ "Entrez Gene: Zinc finger protein 521". https://www.ncbi.nlm.nih.gov/gene/25925.
- ↑ 2.0 2.1 2.2 2.3 "Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells". Blood 103 (6): 2062–2070. March 2004. doi:10.1182/blood-2003-07-2388. PMID 14630787.
- ↑ "A conserved 12-amino acid motif in Sall1 recruits the nucleosome remodeling and deacetylase corepressor complex". The Journal of Biological Chemistry 281 (33): 23922–23931. August 2006. doi:10.1074/jbc.M513461200. PMID 16707490.
- ↑ "Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia". Oncogene 24 (7): 1220–1230. February 2005. doi:10.1038/sj.onc.1208243. PMID 15640894.
- ↑ "The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation". The Journal of Biological Chemistry 284 (6): 3480–3487. February 2009. doi:10.1074/jbc.M805874200. PMID 19074684.
Further reading
- "Early hematopoietic zinc finger protein prevents tumor cell recognition by natural killer cells". Journal of Immunology 182 (8): 4529–37. April 2009. doi:10.4049/jimmunol.0802109. PMID 19342626.
- "Early hematopoietic zinc finger protein-zinc finger protein 521: a candidate regulator of diverse immature cells". The International Journal of Biochemistry & Cell Biology 40 (5): 848–54. 2008. doi:10.1016/j.biocel.2007.04.006. PMID 17543573.
- "Evi3, a common retroviral integration site in murine B-cell lymphoma, encodes an EBFAZ-related Krüppel-like zinc finger protein". Blood 101 (5): 1934–40. March 2003. doi:10.1182/blood-2002-08-2652. PMID 12393497.
- "The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation". The Journal of Biological Chemistry 284 (6): 3480–7. February 2009. doi:10.1074/jbc.M805874200. PMID 19049973.
- "Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells". Blood 103 (6): 2062–70. March 2004. doi:10.1182/blood-2003-07-2388. PMID 14630787.
- "Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions". Pharmacogenomics 13 (4): 399–405. March 2012. doi:10.2217/pgs.11.165. PMID 22379998.
- "Zinc finger protein 521, a new player in bone formation". Annals of the New York Academy of Sciences 1192 (1): 32–7. March 2010. doi:10.1111/j.1749-6632.2009.05347.x. PMID 20392215. Bibcode: 2010NYASA1192...32H.
- "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Molecular Medicine 8 (1): 56–64. January 2002. doi:10.1007/BF03402003. PMID 11984006.
- "Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells". Oncotarget 4 (8): 1280–92. August 2013. doi:10.18632/oncotarget.1176. PMID 23907569.
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