E3 ubiquitin-protein ligase (CHFR) that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. It acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. CHFR is 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. Marked reduction of CHFR expression was detected in primary tumors and decreased CHFR expression was linked to promoter hypermethylation. Restoration of CHFR expression by treatment with the microtubule stress agent nocodazole and the methyltransferase inhibitor 5-aza-2'-deoxycytidine has been reported.
Background References
1. "Epigenetic inactivation of CHFR in human tumors." Toyota M., Sasaki Y., Satoh A., Ogi K., Kikuchi T., Suzuki H., Mita H., Tanaka N., Itoh F., Issa J.-P.J., Jair K.-W., Schuebel K.E., Imai K., Tokino T. Proc. Natl. Acad. Sci. U.S.A. 100:7818-7823(2003)
2. "Chfr is linked to tumour metastasis through the downregulation of HDAC1." Oh Y.M., Kwon Y.E., Kim J.M., Bae S.J., Lee B.K., Yoo S.J., Chung C.H., Deshaies R.J., Seol J.H. Nat. Cell Biol. 11:295-302(2009)
Sequence Similarity
Belongs to the CHFR family.
Tissue Specificity
Ubiquitous.
Post-translational Modification
Poly-ADP-ribosylated. In addition to binding non covalently poly(ADP-ribose) via its PBZ-type zinc finger, the protein is also covalently poly-ADP-ribosylated by PARP1.; Autoubiquitinated; may regulate its cellular level.; Phosphorylated by PKB. Phosphorylation may affect its E3 ligase activity.
Western blot analysis on Hela cell lysates using anti-CHFR rabbit polyclonal antibodies.
ICC staining CHFR in A431 cells (green). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS and counterstained with DAPI in order to highlight the nucleus (blue).
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