Cdk1 is sufficient to drive the mammalian cell cycle

Abstract

Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.

Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas

“…We also explored expression of cell cycle related proteins, and found significant reduction of CYCLIN B1, CDC25A and CDC2. This observation was consistent with previous findings that CDC25A is essential for cell cycle progression from G1 to the S phase through activating the cyclindependent kinase CDC2 by removing two phosphate groups (Boutros et al, 2007;Santamaria et al, 2007). CYCLIN B1, another cell cycle associated protein directly activated by CDC25A, was reported to show markedly various expression through the cell cycle, with its peak level in G2/M phase and lowest level in G1 phase, which was in agreement with our results (Maity et al, 1995).…”

The plant‐specific CDKB 1‐ CYCB 1 complex mediates homologous recombination repair in Arabidopsis

“…The closest homologs of CDC28p in metazoans are Cdk1 and Cdk2. The general dogma is that Cdk2 complexes promote entry and progression through S phase while Cdk1 controls mitosis although Cdk1 can almost completely compensate for the loss of Cdk2 (Santamaría et al , 2007; Malumbres et al , 2009). In particular, Cdk2 was found to play an active role in DNA repair (Deans et al , 2006; Wohlbold et al , 2012).…”

Cdk6-Dependent Regulation of G1 Length Controls Adult Neurogenesis

“…Since recent work by Santamaria et al [71] described a central role for Cdk1 during embryogenesis, it would be interesting to assess if Cdk1 activity also accounts for proliferation in the DG and SVZ as basal levels of both phosphorylation of pRb and cell proliferation are maintained in Cdk6 mutant brains.…”