Cell Biology

Protein Degradation and Growth Regulation

Science's STKE  24 Oct 2006:
Vol. 2006, Issue 358, pp. tw362
DOI: 10.1126/stke.3582006tw362

Controlled protein degradation is a fundamentally important cellular regulatory mechanism. Dorrello et al. searched for binding partners of the ubiquitin ligase SCFβTRCP and detected programmed cell death protein 4 (PDCD4). The growth factor-stimulated protein kinase, S6K1, phosphorylated PDCD4 and promoted its ubiquitination by SCFβTRCP and consequent degradation. The degradation of PDCD4 relieved its inhibitory effect on a translation initiation factor and enhanced protein synthesis. Thus, regulated destruction of PDCD4 appears to regulate cell proliferation and cell size.

N. V. Dorrello, A. Peschiaroli, D. Guardavaccaro, N. H. Colburn, N. E. Sherman, M. Pagano, S6K1- and βTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 314, 467-471 (2006). [Abstract] [Full Text]

N. Sonenberg, A. Pause, Protein synthesis and oncogenesis meet again. Science 314, 428-429 (2006). [Summary] [Full Text]