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

Abstract

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.

ACKNOWLEDGMENTS

We thank J. W. Seo and Y. H. Seo for the generation of ESI-q-TOF tandem MS results and N. P. Dantuma (Karolinska Institutet) for providing the Ub^G76V-GFP clone.

This work was supported by KOSEF through the Center for Cell Signaling Research at Ewha Women's University, by the 21C Frontier Functional Proteomics Center Project (MOST FPR03B3-04-110 and FPR02A7-32-110), and by the National R&D Program for Cancer Control (0420190-1). E.J. Song and S.-H. Yim were supported by the Brain Korea 21 Project.