Is there a role for diacylglycerol kinase-zeta in cell cycle regulation?

Los, A. P., de Widt, J., van Blitterswijk, W. J. and Divecha, N. (2008) Is there a role for diacylglycerol kinase-zeta in cell cycle regulation? Advances in Enzyme Regulation, 48 (1), 31-39. (doi:10.1016/j.advenzreg.2008.02.001).

Abstract

The retinoblastoma tumor suppressor protein (pRB) and its close relatives p107 and p130 aremaster switches in the regulation of developmental processes, including cell cycle regulation,differentiation and apoptosis (Chau and Wang, 2003; Cobrinik, 2005; Nguyen and McCance,2005). During the cell cycle, pRB regulates the G1 to S-phase transition by binding to and inhibiting the activity of the E2F family of transcription factors (Seville et al., 2005). Under optimal conditions for cell division cyclin-dependent kinases (CDKs EC 2.7.11.22)phosphorylate pRB during G1 of the cell cycle, which liberates E2F from its complex withpRB. E2F can then regulate the transcription of genes required for G1eS phase progression.Phosphorylation of pRB in G1 is carried out by cyclin D in complex with CDK4 or CDK6,and cyclin EeCDK2 (Sherr and Roberts, 2004). CyclineCDK complexes, in turn, are regulatedby CDK inhibitors (CKIs). The CIP/KIP family of CKIs, including p21WAF1/CIP1, p27KIP1 andp57KIP2, inhibit cyclin EeCDK complexes, whereas they stabilize and activate cyclin DeCDK4/6 complexes. The INK family of CKIs, including p16INK4a, p15INK4b, p18INK4c andp19INK4d, specifically inhibit CDK4/6 (Sherr and Roberts, 1999). Under several conditions thephosphorylation of pRB is inhibited, enabling the interaction between pRB and E2F and the induction of a G1-arrest. These conditions include depletion of growth factors (Sherr and Roberts,1999), growth inhibitory signals from the TGFb super family, contact inhibition (Li et al., 1995;

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