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Molecular and Cellular Biology, March 2005, p. 2511-2524, Vol. 25, No. 6
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.6.2511-2524.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Fas-Associated Factor 1, Interacting with Ubiquitinated Proteins and Valosin-Containing Protein, Is Involved in the Ubiquitin-Proteasome Pathway

Eun Joo Song,1,{dagger},{ddagger} Seung-Hee Yim,1,{dagger} Eunhee Kim,2 Nam-Soon Kim,3 and Kong-Joo Lee1*

Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul,1 Division of Life Science, Chungnam National University,2 Laboratory of Human Genomics, Division of Genomics and Proteomics, Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea3

Received 11 July 2004/ Returned for modification 25 October 2004/ Accepted 10 November 2004

Human Fas-associated factor 1 (hFAF1) is a novel protein having multiubiquitin-related domains. We investigated the cellular functions of hFAF1 and found that valosin-containing protein (VCP), the multiubiquitin chain-targeting factor in the degradation of the ubiquitin-proteasome pathway, is a binding partner of hFAF1. hFAF1 is associated with the ubiquitinated proteins via the newly identified N-terminal UBA domain and with VCP via the C-terminal UBX domain. The overexpression of hFAF1 and a truncated UBA domain inhibited the degradation of ubiquitinated proteins and increased cell death. These results suggest that hFAF1 binding to ubiquitinated protein and VCP is involved in the ubiquitin-proteasome pathway. We hypothesize that hFAF1 may serve as a scaffolding protein that regulates protein degradation in the ubiquitin-proteasome pathway.

* Corresponding author. Mailing address: Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea. Phone: 82-2-3277-3038. Fax: 82-2-3277-3760. E-mail: kjl{at}ewha.ac.kr.

{dagger} E.J.S. and S.-H.Y. contributed equally to this work.

{ddagger} Present address: Bioanalysis & Biotransformation Research Center, Korea Institute of Science and Technology, Seoul, South Korea.

Molecular and Cellular Biology, March 2005, p. 2511-2524, Vol. 25, No. 6
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.6.2511-2524.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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