CHIP (C3B6) Rabbit mAb

The carboxy terminus of Hsc70-interacting protein (CHIP, STUB1) is a co-chaperone protein and functional E3 ubiquitin ligase that links the polypeptide binding activity of Hsp70 to the ubiquitin proteasome system (1). Cytoplasmic CHIP protein contains three 34-amino acid TPR (tetratricopeptide repeat) domains at its amino terminus and a carboxy-terminal U-box domain. CHIP interacts with the molecular chaperones Hsc70-Hsp70 and Hsp90 through its TPR domain, while E3 ubiquitin ligase activity is confined to the U-box domain (2,3). The binding of CHIP to Hsp70 can stall the folding of Hsp70 client proteins and concomitantly facilitate the U-box dependent ubiquitination of Hsp70-bound substrates (4-6). CHIP appears to play a central role in cell stress protection (7) and is responsible for the degradation of disease-related proteins that include cystic fibrosis transmembrane conductance regulator (4), p53 (8), huntingtin and Ataxin-3 (9), Tau protein (10), and α-synuclein (11). 1.McDonough, H. and Patterson, C. (2003) Cell Stress Chaperones 8, 303-8. 2.Ballinger, C.A. et al. (1999) Mol Cell Biol 19, 4535-45. 3.Murata, S. et al. (2001) EMBO Rep 2, 1133-8. 4.Meacham, G.C. et al. (2001) Nat Cell Biol 3, 100-5. 5.Younger, J.M. et al. (2004) J Cell Biol 167, 1075-85. 6.Jiang, J. et al. (2001) J Biol Chem 276, 42938-44. 7.Dai, Q. et al. (2003) EMBO J 22, 5446-58. 8.Esser, C. et al. (2005) J Biol Chem 280, 27443-8. 9.Jana, N.R. et al. (2005) J Biol Chem 280, 11635-40. 10.Shimura, H. et al. (2004) J Biol Chem 279, 4869-76. 11.Shin, Y. et al. (2005) J Biol Chem 280, 23727-34.