Adaptor proteins play a key role in many physiological processes. We believe that understanding the molecular details of adaptor protein functions through the interactions with other partner proteins can open up new horizons for various therapy strategies. In our laboratory, we work on Bag-1 (Bcl-2 associated athono gene-1) adaptor protein which is the founding member of an anti-apoptotic Bag family. Bag-1 regulates a wide variety of cellular processes, including proliferation, survival, transcription, apoptosis, tumorigenesis and motility. To perform these functions Bag-1 has three functionally distinct isoforms that can interact with a diverse array of molecular targets such as Hsp70/Hsc70 molecular chaperones, components of the ubiquitylation/proteasome machinery, Bcl-2 apoptosis regulator, the Raf-1 kinase, nuclear hormone receptors and DNA. In human malignant cells, the expression of Bag-1 isoforms is frequently altered, and thus their expression profiles may serve as a powerful prognostic/predictive marker in carcinogenesis. Our goal in this project is to delineate the interacting partners of Bag-1 isoforms first in normal cells and later in malignant cells.