Commentary

SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroy

Olena Barbash¹ , Douglas I Lin^1,2 and J Alan Diehl^1,2

¹  The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, Philadelphia, Pennsylvania 19104, USA

²  Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

author email corresponding author email

Cell Division 2007, 2:2doi:10.1186/1747-1028-2-2

Published:	15 January 2007

Abstract

Cyclin D1 is an allosteric regulator for cyclin-dependent kinases 4 and 6 (CDK4/6). The cyclin D/CDK4 kinase promotes G1/S transition through the posttranslational modification and the subsequent inactivation of the retinoblastoma (Rb) protein and related family members (p107 and p130). Accumulation of cyclin D1 is tightly regulated through various mechanisms including transcription, protein localization and ubiquitin-dependent proteolysis. While regulators of cyclin D1 gene expression have been under considerable scrutiny, the identity of the protein complex that targets cyclin D1 protein for degradation, the putative E3 ubiquitin ligase, has remained obscure. In a recent report, Lin et al [1] describe the identification and characterization of a novel SCF, wherein FBX4 and αB-crystallin serve as specificity factors that direct ubiquitination of phosphorylated cyclin D1. As cyclin D1 overexpression in human cancer has been postulated to occur through the loss of degradation machinery, the identification of the SCF^{Fbx4/αB-crystallin} ligase will allow new experimental approaches that address mechanisms of cyclin D1 overexpression in human cancer.