CIZ1 explained

Cip1-interacting zinc finger protein is a protein that in humans is encoded by the CIZ1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a zinc finger DNA binding transcription factor that interacts with CIP1 (p21 / CDKN1A), part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1.^[2]

Clinical significance

An altered circulating form of the Ciz1 protein is synthesized by lung cancer cells, even when they are at a very early stage. Hence detection of this protein variant in blood could be used as a biomarker for early detection of lung cancer.^[3]

Ciz1 mutant mice

Aged (18-mo-old) Ciz1^-/- mice have increased neuronal DNA double-strand breaks that likely contributed to their loss of neurons and cognitive decline with age.^[4] Embryonic fibroblasts from Ciz1^-/- mice show abnormal sensitivity to γ-irradiation with persistent DNA breaks, aberrant cell cycle progression and increased apoptosis.^[4]

Interactions

CIZ1 has been shown to interact with P21.

Further reading

• Lukasik A, Uniewicz KA, Kulis M, Kozlowski P . Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog . The FEBS Journal . 275 . 2 . 332–40 . January 2008 . 18081865 . 10.1111/j.1742-4658.2007.06203.x . 35928583 . free .
• Rahman F, Ainscough JF, Copeland N, Coverley D . Cancer-associated missplicing of exon 4 influences the subnuclear distribution of the DNA replication factor CIZ1 . Human Mutation . 28 . 10 . 993–1004 . October 2007 . 17508423 . 10.1002/humu.20550 . 34590449 . free .
• den Hollander P, Rayala SK, Coverley D, Kumar R . Ciz1, a Novel DNA-binding coactivator of the estrogen receptor alpha, confers hypersensitivity to estrogen action . Cancer Research . 66 . 22 . 11021–9 . November 2006 . 17108141 . 10.1158/0008-5472.CAN-06-2336 . free .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Coverley D, Marr J, Ainscough J . Ciz1 promotes mammalian DNA replication . Journal of Cell Science . 118 . Pt 1 . 101–12 . January 2005 . 15585571 . 10.1242/jcs.01599 . free .
• Warder DE, Keherly MJ . Ciz1, Cip1 interacting zinc finger protein 1 binds the consensus DNA sequence ARYSR(0-2)YYAC . Journal of Biomedical Science . 10 . 4 . 406–17 . 2004 . 12824700 . 10.1159/000071160 . 202648843 .
• Gilley J, Fried M . Extensive gene order differences within regions of conserved synteny between the Fugu and human genomes: implications for chromosomal evolution and the cloning of disease genes . Human Molecular Genetics . 8 . 7 . 1313–20 . July 1999 . 10369878 . 10.1093/hmg/8.7.1313 . free .

Notes and References

1. Mitsui K, Matsumoto A, Ohtsuka S, Ohtsubo M, Yoshimura A . Cloning and characterization of a novel p21(Cip1/Waf1)-interacting zinc finger protein, ciz1 . Biochemical and Biophysical Research Communications . 264 . 2 . 457–64 . October 1999 . 10529385 . 10.1006/bbrc.1999.1516 .
2. Web site: Entrez Gene: CIZ1 CDKN1A interacting zinc finger protein 1.
3. Higgins G, Roper KM, Watson IJ, Blackhall FH, Rom WN, Pass HI, Ainscough JF, Coverley D . 6 . Variant Ciz1 is a circulating biomarker for early-stage lung cancer . Proceedings of the National Academy of Sciences of the United States of America . 109 . 45 . E3128-35 . November 2012 . 23074256 . 3494940 . 10.1073/pnas.1210107109 . free .
4. Khan MM, Xiao J, Patel D, LeDoux MS . DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice . Neurobiology of Aging . 62 . 180–190 . February 2018 . 29154038 . 5877805 . 10.1016/j.neurobiolaging.2017.10.014 .