2xoc

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Template:STRUCTURE 2xoc

Contents

C-TERMINAL CYSTEINE-RICH DOMAIN OF HUMAN CHFR BOUND TO MADPR

Template:ABSTRACT PUBMED 20880844

Function

[CHFR_HUMAN] E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. Promotes the ubiquitination and subsequent degradation of AURKA and PLK1. Probably acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress.[1] [2] [3] [4] [5] [6] [7]

About this Structure

2xoc is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • 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 Dec 10;285(50):39348-58. Epub 2010 Sep 29. PMID:20880844 doi:10.1074/jbc.M110.159855
  1. ↑ Scolnick DM, Halazonetis TD. Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Nature. 2000 Jul 27;406(6794):430-5. PMID:10935642 doi:10.1038/35019108
  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. 2002 Jan 21;156(2):249-59. Epub 2002 Jan 21. PMID:11807090 doi:10.1083/jcb.200108016
  3. ↑ 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 Mar 15;62(6):1797-801. PMID:11912157
  4. ↑ Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene. 2003 Oct 16;22(46):7101-7. PMID:14562038 doi:10.1038/sj.onc.1206831
  5. ↑ Erson AE, Petty EM. CHFR-associated early G2/M checkpoint defects in breast cancer cells. Mol Carcinog. 2004 Jan;39(1):26-33. PMID:14694445 doi:10.1002/mc.10161
  6. ↑ 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 Jan 3;451(7174):81-5. doi: 10.1038/nature06420. PMID:18172500 doi:10.1038/nature06420
  7. ↑ Oh YM, Kwon YE, Kim JM, Bae SJ, Lee BK, Yoo SJ, Chung CH, Deshaies RJ, Seol JH. Chfr is linked to tumour metastasis through the downregulation of HDAC1. Nat Cell Biol. 2009 Mar;11(3):295-302. doi: 10.1038/ncb1837. Epub 2009 Feb 1. PMID:19182791 doi:10.1038/ncb1837

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