Disease relevance of ZNF146

• The human OZF gene (ZNF146), located in chromosome band 19q13.1, is amplified and overexpressed in pancreatic carcinomas [1].
• OZF expression, infrequent or absent in normal colonic mucosa, is present in more than 80% of colorectal cancers [2].
• Immunostaining was observed in low-grade adenomas, indicating that OZF expression occurs very early in the course of tumour progression [2].
• Overexpression of the OZF gene has previously been demonstrated in the majority of pancreatic cancers [2].
• The OZF protein produced in Escherichia coli binds zinc ions, DNA and heparin [3].

High impact information on ZNF146

• Immunohistochemistry revealed OZF expression in tumour cells of 56/59 carcinomas and occasionally in infiltrating lymphocytes but at lower levels [2].
• The zinc finger protein OZF (ZNF146) is overexpressed in colorectal cancer [2].
• Of the 25 tumours analysed by immunoblotting, 20 expressed higher levels of OZF protein than their adjacent normal mucosa [2].
• It contains an open reading frame consisting of 32 amino acid residues followed by ten zinc finger motifs and was accordingly named OZF (Only Zinc Fingers) [4].
• Assuming that translation initiation starts at the unique methionine codon, 22 codons downstream of the beginning of the open reading frame as suggested by in vitro translation of OZF mRNA, the OZF protein is 292 residues long and has an estimated molecular mass of 33 kDa [4].

Biological context of ZNF146

• A Kruppel zinc finger of ZNF 146 interacts with the SUMO-1 conjugating enzyme UBC9 and is sumoylated in vivo [5].
• Mutation of two lysine residues greatly reduced the amount of the sumoylated form of OZF though their surrounding sequences differ from the consensus sequence reported for most proteins modified by SUMO-1 conjugation [5].
• ZNF146 encompasses 25 kb of sequence and consists of four non-coding exons located upstream of a single coding exon [6].
• The sequence of proximal 1.4 kb of ZNF146 promoter has a high GC content, is devoid of a TATA box and contains several potential transcriptional elements [6].
• The OZF gene is located in band q13.1 of the long arm of human chromosome 19 [4].

Anatomical context of ZNF146

• The presence of the sumoylated form in HeLa cells solely transfected by OZF indicates the physiological activity of the endogenous SUMO-1 conjugation pathway [5].
• Expression was detected in all cell lines, and the gene was over-expressed in cell lines with OZF gene amplification [7].
• Five of 8 tumours, including 2 primary tumours with OZF gene amplification, displayed high levels of OZF protein, whereas normal pancreas expressed low levels [7].
• In addition, OZF protein overexpression was found in a tumor cell line, which suggests a possible involvement in carcinogenesis [3].

Physical interactions of ZNF146

• The three zinc fingers at the C-terminus of OZF interact with a region of hRap1 located downstream of the coil domain [8].

References