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Chfr is linked to tumour metastasis through the downregulation of HDAC1

Oh, Young Mi and Kwon, Young Eun and Kim, Joo Mi and Bae, Sung Jun and Lee, Bo Keun and Yoo, Soon Ji and Chung, Chin Ha and Deshaies, Raymond J. and Seol, Jae Hong (2009) Chfr is linked to tumour metastasis through the downregulation of HDAC1. Nature Cell Biology, 11 (3). pp. 295-302. ISSN 1465-7392.

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Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. It has been suggested that Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To better understand how Chfr activity relates to cell-cycle progression and tumorigenesis, we sought to identify Chfr-interacting proteins using affinity purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in cancer cells that normally do not express it results in downregulation of HDAC1, leading to upregulation of the Cdk inhibitor p21^(CIP1/WAF1) and the metastasis suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in the G1 phase of the cell cycle and become less invasive. Collectively, our data suggest that Chfr functions as a tumour suppressor by regulating HDAC1.

Item Type:Article
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Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2009 Nature Publishing Group. Received 27 August 2008; accepted 4 November 2008; published online 1 February 2009. We thank S. H. Baek (SNU) for reagents. This work was supported by grants from the Korea Science and Engineering Foundation (M10533010001‑07N3301‑00110), the SRC program (R11‑2005‑009‑02002‑0), the Korea Research Foundation (KRF-2002-015-CS0069) and the BK21 program. Y.E.K. was supported by the Seoul Science Fellowship.
Funding AgencyGrant Number
Korea Science and Engineering FoundationM10533010001-07N3301-00110
Scientific Research Corporation (SRC) programR11-2005-009-02002-0
Korea Research FoundationKRF2002-015-CS0069
Seoul Science FellowshipUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20090529-100421943
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14340
Deposited By: Tony Diaz
Deposited On:03 Jun 2009 16:01
Last Modified:03 Oct 2019 00:49

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