A Cyclin-Dependent Kinase Inhibitor, Dacapo, Is Necessary for Timely Exit from the Cell Cycle during Drosophila Embryogenesis

Abstract

In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap expression in embryos parallels the exit of cells from the cell cycle. dap mutant embryos delay the normal cell cycle exit during development; many cells complete an additional cycle and subsequently become quiescent. Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle.

The Drosophila wing differentiation factor Vestigial–Scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc

“…27,28 To clearly establish the role of vg and sd in proliferation, we overexpressed the Drosophila Dacapo (DAP) protein which shares strong homology with human p21. 29 Human p21 has been shown to inhibit cyclin-CDK complexes, Rb phosphorylation and therefore E2F1 factor activation of its target genes. In most cases examined, p21 is essential for G1 arrest before differentiation of cells.…”

Ectopic expression of human p53 inhibits entry into S phase and induces apoptosis in the Drosophila eye imaginal disc

“…Recently, a Drosophila gene, dacapo has been identi®ed as a member of the p21/p27 family of cdk inhibitors (de Nooij et al, 1996). We crossed the transgenic lines expressing p53 with a de®ciency line, Df(2R)B5[46A; 46C] lacking the dacapo locus, 46B1-2, or dacapo mutant lines (dap 4 and dap 4454 ), but no signi®cant e ect on the p53-induced rough eye phenotype was observed (Figure 11, data not shown).…”

“…An enhancer trap line H214 with a P-element insertion at the klingon locus (Butler et al, 1997) was kindly provided by Dr Y Hiromi. Dacapo mutant strains, dap 4 and dap 4454 were kindly provided by Dr I Hariharan (de Nooij et al, 1996). Transgenic¯y lines carrying pGMR-P35 was kindly provided by Dr B Hay (Hay et al, 1994).…”

Retinoblastoma family genes

“…Characterization of the phenotypes of embryos devoid of RBF revealed that RBF is required for the repression of E2F target gene expression and for maintaining the first G1 cell cycle arrest during embryonic development (Du and Dyson, 1999). This establishment of the first G1 cell cycle arrest in the developing embryos requires Dacapo, the only member of the p21/p27 family of cdk inhibitors in Drosophila (de Nooij et al, 1996;Lane et al, 1996). Therefore, Rb and the p21/p27 family of cdk inhibitors function cooperatively to achieve a stable G1 cell cycle arrest during fly embryonic development.…”