Biology:UHRF1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the UHRF1 gene.

Function

This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to hemi-methylated DNA during S-phase and recruits the main DNA methyltransferase protein, DNMT1, to regulate chromatin structure and gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition, and functions in the p53-dependent DNA damage checkpoint. Multiple transcript variants encoding different isoforms have been found for this gene. It was originally identified as a direct regulator of topoisomerase 2a, but this has subsequently been disproven. Uhrf1 has been extensively studied in vivo using zebrafish.

Clinical significance

UHRF1 has recently been identified as a novel oncogene in hepatocellular carcinoma, the primary type of liver cancer.

Further reading

• "A new growth-regulated complementary DNA with the sequence of a putative trans-activating factor". Cell Growth & Differentiation 2 (4): 179–86. Apr 1991. PMID 1868030. 
• "Generation and analysis of 280,000 human expressed sequence tags". Genome Research 6 (9): 807–28. September 1996. doi:10.1101/gr.6.9.807. PMID 8889549. 
• "ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression". Cancer Research 60 (1): 121–8. Jan 2000. PMID 10646863. 
• "Genomic structure and chromosomal mapping of the gene coding for ICBP90, a protein involved in the regulation of the topoisomerase IIalpha gene expression". Gene 266 (1–2): 15–23. Mar 2001. doi:10.1016/S0378-1119(01)00371-7. PMID 11290415. 
• "ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells". British Journal of Cancer 89 (1): 120–7. Jul 2003. doi:10.1038/sj.bjc.6601068. PMID 12838312. 
• "Np95 is a histone-binding protein endowed with ubiquitin ligase activity". Molecular and Cellular Biology 24 (6): 2526–35. Mar 2004. doi:10.1128/MCB.24.6.2526-2535.2004. PMID 14993289. 
• "Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition". Genes to Cells 9 (2): 131–42. Feb 2004. doi:10.1111/j.1356-9597.2004.00710.x. PMID 15009091. 
• "ICBP90 expression is downregulated in apoptosis-induced Jurkat cells". Annals of the New York Academy of Sciences 1010 (1): 300–3. December 2003. doi:10.1196/annals.1299.052. PMID 15033738. Bibcode: 2003NYASA1010..300A. 
• "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology 22 (6): 707–16. June 2004. doi:10.1038/nbt971. PMID 15146197. 
• "Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase IIalpha expression". Biochemical and Biophysical Research Communications 319 (2): 590–5. June 2004. doi:10.1016/j.bbrc.2004.05.028. PMID 15178447. 
• "ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain". Oncogene 23 (46): 7601–10. Oct 2004. doi:10.1038/sj.onc.1208053. PMID 15361834. 
• "TCR pathway involves ICBP90 gene down-regulation via E2F binding sites". Biochemical Pharmacology 70 (4): 570–9. Aug 2005. doi:10.1016/j.bcp.2005.05.012. PMID 15964557. 
• "The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle". Oncogene 24 (49): 7337–45. Nov 2005. doi:10.1038/sj.onc.1208878. PMID 16007129. 
• "Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth". Molecular Biology of the Cell 16 (12): 5621–9. December 2005. doi:10.1091/mbc.E05-03-0194. PMID 16195352. 
• "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. Jan 2006. doi:10.1101/gr.4039406. PMID 16344560. 
• "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. Oct 2006. doi:10.1038/nbt1240. PMID 16964243. 
• "Isolation and Characterization of a Novel Human Radiosusceptibility Gene, NP95". Radiation Research 166 (5): 723–33. Nov 2006. doi:10.1667/RR0459.1. PMID 17067204. Bibcode: 2006RadR..166..723M.