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American Public Health Association
133rd Annual Meeting & Exposition
December 10-14, 2005
Philadelphia, PA
APHA 2005
 
3063.1: Monday, December 12, 2005 - Board 5

Abstract #119032

Determining the Cellular Function of Cullin 5 Containing E3 Ubiquitin Ligase

Elana Ehrlich, Johns Hopkins Bloomberg School of Public Health, 622 N. Washington St., 5th floor, MMI, Baltimore, MD 21205, 410.614.4273, ccrimmins@asph.org

Regulated protein turnover is one mechanism by which the cell regulates critical processes such as mitosis and the cell cycle. The specificity of protein degradation is mediated by members of the E3 ubiquitin ligase family, one of which is the ElonginB/C-Cullin5-SOCS-box (ECS) E3 ligase. Our lab has demonstrated that HIV-1 Vif uses a Cul5-ElonginB-ElonginC E3 ligase to degrade the cellular antiviral proteins, APOBEC3G and APOBEC3F. Currently, the normal cellular function of Cul5 is unclear. In order to utilize the Vif-E3 interaction as a target for antiviral therapy, we must be aware of potential conflicts with normal cellular function. In addition, the effect of Vif on the cellular function of the Cul5 E3 ligase remains uncertain. In order to address these issues we have identified Hsp70 in a search for Cul5 interacting proteins. Here we demostrate that Hsp70 and Cul5 are involved in the degradation of Hsp90 client proteins, specifically the cell surface receptor ErbB2. Geldanamycin (GA), a potent Hsp90 ATPase inhibitor, has been shown to induce the degradation of Hsp90 client proteins. While the E3 ligase, CHIP, has been implicated with Hsc70 in GA induced ErbB2 degradation, protein stability is incomplete in CHIP-/- cells, suggesting an additional E3 is involved in ErbB2 turnover. Here we demonstrate that Hsp70 interacts with members of the Cul5 E3 ligase complex and that GA induced degradation of ErbB2 requires the presence of Cul5 and Hsp70.

Learning Objectives:

Keywords: Cancer,

Presenting author's disclosure statement:

I wish to disclose that I have NO financial interests or other relationship with the manufactures of commercial products, suppliers of commercial services or commercial supporters.

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The 133rd Annual Meeting & Exposition (December 10-14, 2005) of APHA