Cell and Tissue Signaling

Tuesday, October 18, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP241) Role of molecular chaperone Bag-3/ CAIR-1 in the regulation of Akt and its related proteins following irradiation.

D'Cruz, Genevieve1, 2, Gius, David 1, 4, Morgan, William1, 2, 3, 1 Molecular and Cell Biology Graduate Program, Baltimore, Maryland, USA2 Department of Radiation Oncology, Baltimore, Maryland, USA4 Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA3 Marlene and Stewart Greenbaum Cancer Center, Baltimore, Maryland, USA

ABSTRACT- Bag-3/CAIR-1 is a molecular co-chaperone involved in regulating Hsp 70 activity. The bag domain of Bag-3/CAIR-1 binds to the ATPase domain of Hsp 70, regulating Hsp 70 activity. Heat shock protein complexes like Hsp 70 and Hsp 90 are involved in optimal folding and facilitating the removal of damaged proteins to the proteasome for degradation. In breast cancer cells (MDA435) that overexpress either the full length (FL) or bag domain deleted (dBag) forms of Bag-3/CAIR-1, there is differential regulation of Akt and its downstream binding partners (GSK3beta, CREB, and P70S6 kinase) post irradiation at low doses versus high doses. Bag-3/CAIR-1 may play a role in inhibiting Akt related protein degradation in an Hsp 70 dependent manner. Future studies will investigate the role of Bag-3/CAIR-1 in inhibiting protein degradation following a time course of irradiation and at different doses. The precise point at which CAIR-1/Bag-3 functions to regulate the signaling process will also be investigated. Additionally, the ubiquitination status of Akt family members and partner proteins will also be studied.

Key words: Bag-3/CAIR-1, Akt, Hsp70, Hsp90

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2005 RRS