NOVEL COMPONENT OF VON HIPPEL-LINDAU TUMOR SUPPRESSOR COMPLEX AND SCF UBIQUITIN LIGASE

摘要

Rbx1, an evolutionarily conserved Cullin-interacting RING-H2 finger protein, has been discovered. Mammalian Rbx1 has been identified as a component of th e CUL2-containing VHL complex. An Rbx1 homolog from S. cerevisiae has also bee n identified as a subunit and activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cdk inhibitor Sicl and f or the G1/S cell cycle transition in yeast, providing a link between the multiprotein VHL tumor suppressor complex and cellular ubiquitination. The Rbx1 protein acts as a cellular marker useful (1) in detecting a possible predisposition to certain carcinomas, (2) as a molecular target for treating those carcinomas therapeutically, (3) as a target for inhibition by drugs th at manipulate the growth of cells, and (4) as a research tool to better understand the various complex mechanisms of cell ubiquitination, binding of certain activator proteins, fibronectin deposition and other aspects of the cellular division process.