Historical Background
Chfr (Checkpoint with FHA and RING domains) is a ubiquitously expressed E3 ubiquitin ligase that is involved in a mitotic cell cycle checkpoint. It was identified from an expressed sequence tag (EST) database search for proteins containing forkhead-associated (FHA) motifs (Scolnick and Halazonetis 2000). Protein BLAST comparison revealed that Chfr is conserved across species, from unicellular eukaryotic yeast cell, Schizosaccharomyces pombe and Saccharomyces cerevisiaeto mice. Chfr orthologues in yeast, Dma1 and its paralog, Dma2, have been shown to be involved in regulating various cell division cycle processes such as spindle assembly, spindle positioning, and cytokinesis. More significantly, Dma1 and Dma2 were also demonstrated to regulate mitotic exit in fission yeast and budding yeast via SIN (Septation Initiation Network) and MEN (Mitotic Exit Network) respectively (analogous to...
References
Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature. 2008;451:81–5.
Bae SJ, Kwon YE, Kim M, Seol JH. CHFR is negatively regulated by SUMOylation-mediated ubiquitylation. Biochem Biophys Res Commun. 2013;433:194–9.
Brodie SA, Li G, Harvey D, Khuri FR, Vertino PM, Brandes JC. Small molecule inhibition of the CHFR-PARP1 interaction as novel approach to overcome intrinsic taxane resistance in cancer. Oncotarget. 2015;6:30773–86.
Burgess A, Labbe JC, Vigneron S, Bonneaud N, Strub JM, Van Dorsselaer A, Lorca T, Castro A. Chfr interacts and colocalizes with TCTP to the mitotic spindle. Oncogene. 2008;27:5554–66.
Chaturvedi P, Sudakin V, Bobiak ML, Fisher PW, Mattern MR, Jablonski SA, Hurle MR, Zhu Y, Yen TJ, Zhou BB. Chfr regulates a mitotic stress pathway through its RING-finger domain with ubiquitin ligase activity. Cancer Res. 2002;62:1797–801.
Chin CF, Yeong FM. Safeguarding entry into mitosis: the antephase checkpoint. Mol Cell Biol. 2010;30:22–32.
Hergovich A, Hemmings BA. Hippo signalling in the G2/M cell cycle phase: lessons learned from the yeast MEN and SIN pathways. Semin Cell Dev Biol. 2012;23:794–802.
Kashima L, Idogawa M, Mita H, Shitashige M, Yamada T, Ogi K, Suzuki H, Toyota M, Ariga H, Sasaki Y, Tokino T. CHFR protein regulates mitotic checkpoint by targeting PARP-1 protein for ubiquitination and degradation. J Biol Chem. 2012;287:12975–84.
Kim JS, Park YY, Park SY, Cho H, Kang D, Cho H. The auto-ubiquitylation of E3 ubiquitin-protein ligase Chfr at G2 phase is required for accumulation of polo-like kinase 1 and mitotic entry in mammalian cells. J Biol Chem. 2011;286:30615–23.
Kwon YE, Bae SJ, Kim M, Seol JH. SUMOylation negatively regulates the stability of CHFR tumor suppressor. Biochem Biophys Res Commun. 2013;430:213–7.
Liu C, Wu J, Paudyal SC, You Z, Yu X. CHFR is important for the first wave of ubiquitination at DNA damage sites. Nucleic Acids Res. 2013;41:1698–710.
Maddika S, Sy SM, Chen J. Functional interaction between Chfr and Kif22 controls genomic stability. J Biol Chem. 2009;284:12998–3003.
Matsusaka T, Pines J. Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells. J Cell Biol. 2004;166:507–16.
Oberoi J, Richards MW, Crumpler S, Brown N, Blagg J, Bayliss R. Structural basis of poly(ADP-ribose) recognition by the multizinc binding domain of checkpoint with forkhead-associated and RING Domains (CHFR). J Biol Chem. 2010;285:39348–39358.
Perdereau D, Cailliau K, Browaeys-Poly E, Lescuyer A, Carre N, Benhamed F, Goenaga D, Burnol AF. Insulin-induced cell division is controlled by the adaptor Grb14 in a Chfr-dependent manner. Cell Signal. 2015;27:798–806.
Privette LM, Weier JF, Nguyen HN, Yu X, Petty EM. Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint. Neoplasia. 2008;10:643–52.
Sanbhnani S, Yeong FM. CHFR: a key checkpoint component implicated in a wide range of cancers. Cell Mol Life Sci. 2012;69:1669–1687.
Scolnick DM, Halazonetis TD. Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Nature. 2000;406:430–5.
Shinde SR, Gangula NR, Kavela S, Pandey V, Maddika S. TOPK and PTEN participate in CHFR mediated mitotic checkpoint. Cell Signal. 2013;25:2511–7.
Wu J, Chen Y, Lu LY, Wu Y, Paulsen MT, Ljungman M, Ferguson DO, Yu X. Chfr and RNF8 synergistically regulate ATM activation. Nat Struct Mol Biol. 2011;18:761–8.
Yu X, Minter-Dykhouse K, Malureanu L, Zhao WM, Zhang D, Merkle CJ, Ward IM, Saya H, Fang G, van Deursen J, Chen J. Chfr is required for tumor suppression and Aurora A regulation. Nat Genet. 2005;37:401–6.
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YFM is funded by the Singapore Ministry of Education Tier 2 grant (R183-000-328-112).
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Chin, C.F.C., Yeong, F.M. (2016). CHFR. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101581-1
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DOI: https://doi.org/10.1007/978-1-4614-6438-9_101581-1
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