Alternative titles; symbolsZINC FINGER AND BRCA1-INTERACTING PROTEIN WITH A KRAB DOMAIN 1; ZBRK1HGNC Approved Gene Symbol: ZNF350Cytogenetic location: 19q13.41 ...
Alternative titles; symbols
HGNC Approved Gene Symbol: ZNF350
Cytogenetic location: 19q13.41 Genomic coordinates (GRCh38): 19:51,964,339-51,986,855 (from NCBI)
▼ Cloning and Expression
BRCA1 (113705) is implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, Zheng et al. (2000) performed a yeast 2-hybrid screen for proteins associated with BRCA1 and isolated a cDNA encoding ZBRK1. The 60-kD, 532-amino acid ZBRK1 protein contains an N-terminal KRAB domain and 8 consecutive Kruppel-type C2H2 zinc finger motifs within its central region.
▼ Gene Function
Zheng et al. (2000) stated that ZBRK1 binds to a specific sequence, GGGxxxCAGxxxTTT, within GADD45 (126335) intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. Through this recognition sequence, ZBRK1 represses transcription in a BRCA1-dependent manner. The results revealed a novel corepressor function for BRCA1 and provided a mechanistic basis for the biologic activity of BRCA1 through sequence-specific transcriptional regulation.
Yun and Lee (2003) found that ZBRK1 is rapidly degraded upon treatment of an osteosarcoma cell line with the DNA-damaging agents, ultraviolet light and methyl methanesulfonate. Inhibitors of the ubiquitin-proteasome pathway blocked degradation of ZBRK1. The authors identified a 44-amino acid element between the KRAB domain and the 8 zinc fingers of ZBRK1 that was sufficient for the DNA damage-induced degradation of ZBRK1. Cells expressing this mutant were hypersensitive to DNA damage and were compromised for GADD45 derepression.
▼ Molecular Genetics
Rutter et al. (2003) studied 2 potential breast cancer susceptibility genes that encode the BRCA1-interacting proteins ZNF350 and BRIP1, or BACH1 (603882). They sequenced ZNF350 and BRIP1 in probands from 21 families with potentially inherited breast-ovarian cancer, all of whom were negative for mutations in BRCA1 or BRCA2 (600185). A ZNF350 missense mutation was identified in the proband of one high-risk family, but no other family members were available for testing. Rutter et al. (2003) concluded that it is unlikely that mutations in these genes account for a significant fraction of inherited breast cancer.