CHFR explained

E3 ubiquitin-protein ligase CHFR is an enzyme that in humans is encoded by the CHFR gene.^{[1] [2] [3]}

CHFR is recruited to sites of DNA damage and participates in the DNA damage response. CHFR has an important role in the survival of male premeiotic germ cells.^[4] About 30% of male CHFR knockout mice are infertile.^[4] In these knockout mice spermatogenesis onset is delayed and apoptosis in premeiotic germ cells is significantly increased. When these mice are 3 months old there is a complete loss of germ cells in their testes.

Further reading

• Chaturvedi P . Chfr regulates a mitotic stress pathway through its RING-finger domain with ubiquitin ligase activity . Cancer Res. . 62 . 6 . 1797–801 . 2002 . 11912157 . Sudakin V . Bobiak ML . 3 . Fisher . PW . Mattern . MR . Jablonski . SA . Hurle . MR . Zhu . Y . Yen . TJ .
• Mizuno K . Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers . Oncogene . 21 . 15 . 2328–33 . 2002 . 11948416 . 10.1038/sj.onc.1205402 . Osada H . Konishi H . 3 . Tatematsu . Yoshio . Yatabe . Yasushi . Mitsudomi . Tetsuya . Fujii . Yoshitaka . Takahashi . Takashi . 1447106 .
• Stavridi ES . Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate . Structure . 10 . 7 . 891–9 . 2002 . 12121644 . 10.1016/S0969-2126(02)00776-1 . Huyen Y . Loreto IR . 3 . Scolnick . Daniel M. . Halazonetis . Thanos D. . Pavletich . Nikola P. . Jeffrey . Philip D. . free .
• Shibata Y . Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer . Carcinogenesis . 23 . 10 . 1695–9 . 2002 . 12376479 . 10.1093/carcin/23.10.1695 . Haruki N . Kuwabara Y . 3 . Ishiguro . H . Shinoda . N . Sato . A . Kimura . M . Koyama . H . Toyama . T . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Corn PG . Frequent hypermethylation of the 5' CpG island of the mitotic stress checkpoint gene Chfr in colorectal and non-small cell lung cancer . Carcinogenesis . 24 . 1 . 47–51 . 2003 . 12538348 . 10.1093/carcin/24.1.47 . Summers MK . Fogt F . 3 . Virmani . AK . Gazdar . AF . Halazonetis . TD . El-Deiry . WS . free .
• Toyota M . Epigenetic inactivation of CHFR in human tumors . Proc. Natl. Acad. Sci. U.S.A. . 100 . 13 . 7818–23 . 2003 . 12810945 . 10.1073/pnas.1337066100 . 164671 . Sasaki Y . Satoh A . 3 . Ogi . K . Kikuchi . T . Suzuki . H . Mita . H . Tanaka . N . Itoh . F . 2003PNAS..100.7818T . free .
• Bothos J . The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains . Oncogene . 22 . 46 . 7101–7 . 2003 . 14562038 . 10.1038/sj.onc.1206831 . Summers MK . Venere M . 3 . Scolnick . Daniel M . Halazonetis . Thanos D . 34904290 .
• Mariatos G . Inactivating mutations targeting the chfr mitotic checkpoint gene in human lung cancer . Cancer Res. . 63 . 21 . 7185–9 . 2004 . 14612512 . Bothos J . Zacharatos P . 3 . Summers . MK . Scolnick . DM . Kittas . C . Halazonetis . TD . Gorgoulis . VG .
• Shtivelman E . Promotion of mitosis by activated protein kinase B after DNA damage involves polo-like kinase 1 and checkpoint protein CHFR . Mol. Cancer Res. . 1 . 13 . 959–69 . 2004 . 14638868 .
• Bertholon J . Chfr inactivation is not associated to chromosomal instability in colon cancers . Oncogene . 22 . 55 . 8956–60 . 2004 . 14654793 . 10.1038/sj.onc.1207078 . Wang Q . Falette N . 3 . Verny . Carole . Auclair . Jessie . Chassot . Christelle . Navarro . Claudine . Saurin . Jean-Christophe . Puisieux . Alain . 8538887 .
• Erson AE, Petty EM . CHFR-associated early G2/M checkpoint defects in breast cancer cells . Mol. Carcinog. . 39 . 1 . 26–33 . 2004 . 14694445 . 10.1002/mc.10161 . 2027.42/35063 . 25674441 . free .
• Satoh A . Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer . Cancer Res. . 63 . 24 . 8606–13 . 2004 . 14695171 . Toyota M . Itoh F . 3 . Sasaki . Y . Suzuki . H . Ogi . K . Kikuchi . T . Mita . H . Yamashita . T .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Kang HC . Promoter hypermethylation and silencing of CHFR mitotic stress checkpoint gene in human gastric cancers . Oncol. Rep. . 12 . 1 . 129–33 . 2005 . 15201973 . 10.3892/or.12.1.129. Kim IJ . Park JH . 3 . Shin . Y . Park . HW . Ku . JL . Yang . HK . Lee . KU . Choe . KJ .
• Matsusaka T, Pines J . Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells . J. Cell Biol. . 166 . 4 . 507–16 . 2004 . 15302856 . 10.1083/jcb.200401139 . 2172205 .
• Daniels MJ, Marson A, Venkitaraman AR . PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein . Nat. Struct. Mol. Biol. . 11 . 11 . 1114–21 . 2004 . 15467728 . 10.1038/nsmb837 . 246702 .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .

Notes and References

1. Scolnick DM, Halazonetis TD . Chfr defines a mitotic stress checkpoint that delays entry into metaphase . Nature . 406 . 6794 . 430–5 . Aug 2000 . 10935642 . 10.1038/35019108 . 2000Natur.406..430S . 4401185 .
2. Kang D, Chen J, Wong J, Fang G . The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition . J Cell Biol . 156 . 2 . 249–59 . Jan 2002 . 11807090 . 2199220 . 10.1083/jcb.200108016 .
3. Web site: Entrez Gene: CHFR checkpoint with forkhead and ring finger domains. .
4. 26566864 . 2015 . Lu . L. Y. . Yu . X. . CHFR is important for the survival of male premeiotic germ cells . Cell Cycle . 14 . 21 . 3454–3460 . 10.1080/15384101.2015.1093701 . 4825563 .