SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroy.
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 describe the identification and characterization of a novel SCF, wherein FBX4 and alphaB-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 SCFFbx4/alphaB-crystallin ligase will allow new experimental approaches that address mechanisms of cyclin D1 overexpression in human cancer.
Barbash
Olena
O
Lin
Douglas I
DI
Diehl
J Alan
JA