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ZNF350  -  zinc finger protein 350

Homo sapiens

Synonyms: KRAB zinc finger protein ZFQR, ZBRK1, ZFQR, Zinc finger and BRCA1-interacting protein with a KRAB domain 1, Zinc finger protein 350, ...
 
 
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Disease relevance of ZNF350

  • Based on sequencing of ZBRK1 and BRIP1 in 21 BRCA1/2-negative probands from inherited breast/ovarian cancer families, it appears unlikely that mutations in these genes account for a significant fraction of inherited breast cancer [1].
  • These experiments identify ZBRK1 as another cell protein that, through BBLF2/3, provides a tethering point on oriLyt for the EBV replication complex [2].
  • Altered expression of the ZBRK1 gene in human breast carcinomas [3].
 

High impact information on ZNF350

  • ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner [4].
  • By analysis of a series of ZBRK1 mutants, a 44-amino-acid element located between the N-terminal KRAB domain and the eight zinc fingers was found to be sufficient for the DNA damage-induced degradation of ZBRK1 [5].
  • However, it is unclear how transcription repression by ZBRK1 is relieved subsequent to DNA damage [5].
  • In addition, ZBRK1-binding sequences are located at the regulatory region of many DNA damage-inducible genes, suggesting that ZBRK1 may have a role in DNA damage response [5].
  • Here we report that ZBRK1 is rapidly degraded upon treatment with the DNA-damaging agents UV and methyl methanesulfonate [5].
 

Biological context of ZNF350

 

Anatomical context of ZNF350

  • The KRAB domain is also required for the transcriptional repression activity of ZFQR and in maintaining association of the protein with the nuclear matrix [7].
 

Physical interactions of ZNF350

 

Other interactions of ZNF350

 

Analytical, diagnostic and therapeutic context of ZNF350

References

  1. Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals. Rutter, J.L., Smith, A.M., Dávila, M.R., Sigurdson, A.J., Giusti, R.M., Pineda, M.A., Doody, M.M., Tucker, M.A., Greene, M.H., Zhang, J., Struewing, J.P. Hum. Mutat. (2003) [Pubmed]
  2. The Epstein-Barr virus replication protein BBLF2/3 provides an origin-tethering function through interaction with the zinc finger DNA binding protein ZBRK1 and the KAP-1 corepressor. Liao, G., Huang, J., Fixman, E.D., Hayward, S.D. J. Virol. (2005) [Pubmed]
  3. Altered expression of the ZBRK1 gene in human breast carcinomas. Garcia, V., Domínguez, G., García, J.M., Silva, J., Peña, C., Silva, J.M., Carcereny, E., Menendez, J., España, P., Bonilla, F. J. Pathol. (2004) [Pubmed]
  4. Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1. Zheng, L., Pan, H., Li, S., Flesken-Nikitin, A., Chen, P.L., Boyer, T.G., Lee, W.H. Mol. Cell (2000) [Pubmed]
  5. Degradation of transcription repressor ZBRK1 through the ubiquitin-proteasome pathway relieves repression of Gadd45a upon DNA damage. Yun, J., Lee, W.H. Mol. Cell. Biol. (2003) [Pubmed]
  6. Tetrameric oligomerization mediates transcriptional repression by the BRCA1-dependent Kruppel-associated box-zinc finger protein ZBRK1. Tan, W., Kim, S., Boyer, T.G. J. Biol. Chem. (2004) [Pubmed]
  7. Characterization of a novel zinc finger gene with increased expression in nondividing normal human cells. Ran, Q., Wadhwa, R., Bischof, O., Venable, S., Smith, J.R., Pereira-Smith, O.M. Exp. Cell Res. (2001) [Pubmed]
  8. Functional dissection of transcription factor ZBRK1 reveals zinc fingers with dual roles in DNA-binding and BRCA1-dependent transcriptional repression. Tan, W., Zheng, L., Lee, W.H., Boyer, T.G. J. Biol. Chem. (2004) [Pubmed]
  9. Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. García-Closas, M., Egan, K.M., Newcomb, P.A., Brinton, L.A., Titus-Ernstoff, L., Chanock, S., Welch, R., Lissowska, J., Peplonska, B., Szeszenia-Dabrowska, N., Zatonski, W., Bardin-Mikolajczak, A., Struewing, J.P. Hum. Genet. (2006) [Pubmed]
  10. A common DNA-binding site for SZF1 and the BRCA1-associated zinc finger protein, ZBRK1. Peng, H., Zheng, L., Lee, W.H., Rux, J.J., Rauscher, F.J. Cancer Res. (2002) [Pubmed]
  11. Doxorubicin down-regulates Kruppel-associated box domain-associated protein 1 sumoylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells. Lee, Y.K., Thomas, S.N., Yang, A.J., Ann, D.K. J. Biol. Chem. (2007) [Pubmed]
  12. The GADD45, ZBRK1 and BRCA1 pathway: quantitative analysis of mRNA expression in colon carcinomas. Garcia, V., García, J.M., Peña, C., Silva, J., Domínguez, G., Rodríguez, R., Maximiano, C., Espinosa, R., España, P., Bonilla, F. J. Pathol. (2005) [Pubmed]
 
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