PMID:22876279

Citation	Lee, JJ, Kim, YM, Jeong, J, Bae, DS and Lee, KJ (2012) Ubiquitin-associated (UBA) domain in human Fas associated factor 1 inhibits tumor formation by promoting Hsp70 degradation. PLoS ONE 7:e40361
Abstract	Human Fas associated factor 1 (hFAF1) is a pro-apoptotic scaffolding protein containing ubiquitin-associating (UBA), ubiquitin like 1 and 2 (UBL1, UBL2), and ubiquitin regulatory X (UBX) domains. hFAF1 interacts with polyubiquitinated proteins via its N-terminal UBA domain and with valosin containing protein (VCP) via its C-terminal UBX domain. Overexpression of hFAF1 or its N-terminal UBA domain significantly increases cell death by increasing the degradation of polyubiquitinated proteins. In this study, we investigated whether hFAF1, whose expression level is reduced in cervical cancer, plays a role in tumor formation. We found that HeLa cells overexpressing full-length hFAF1 or the hFAF1 UBA domain alone, significantly suppressed the anchorage independent tumor growth in soft agar colony formation, increased cell death, and activated JNK and caspase 3. Employing UBA-specific tandem immunoprecipitation, we identified moieties specifically interacting with UBA domain of hFAF1, and found that polyubiquitinated Hsp70s are recruited to UBA domain. We also demonstrated that hFAF1 overexpression promotes Hsp70 degradation via the proteasome. We further found that mutating the UBA domain (I41N), as well as knocking down hFAF1 with specific RNAi, abolishs its ability to increase the proteasomal degradation of Hsp70. These findings suggest that hFAF1 inhibits tumor formation by increasing the degradation of Hsp70 mediated via its UBA domain.
Links	PubMed PMC3410879 Online version:10.1371/journal.pone.0040361
Keywords	Adaptor Proteins, Signal Transducing/chemistry; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Cell Death/genetics; Cell Line, Tumor; Cell Proliferation; Gene Expression; Gene Silencing; HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Neoplasms/genetics; Neoplasms/metabolism; Protein Binding; Protein Interaction Domains and Motifs/genetics; Proteolysis; Ubiquitination
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FAF1		GO:0008219: cell death	ECO:0000315:		P		Figure 4 B & C shows the pro-apoptosis abilities of hFAF1. The plates show that in those cells where hFAF1 was knocked out there was a significant increase in cell growth, in contrast those plates where the hFAF1 was left functioning properly there was a lack of cell growth, which was due to hFAF1 ability to break down HSP 70. This is again shown in the table, which specifically points out the amount of colonies.	complete CACAO 9784

References

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