Escaping death to quiescence

Cancer recurrence is associated with treatment failure and is the main cause of death, 1 and thus remains to be a major clinical challenge. elevated level of the cyclin-dependent kinase 1 (CDK1) correlates with cancer recurrence and treatment resistance in patients with breast cancer or colorectal cancer. 2,3 it is proposed that defects in CDKs may lead to the accumulated genetic defects, which render cells less sensitive to drug-induced growth inhibition and apoptosis. 4 CDK1 is the most essential CDK, as it alone is sufficient to drive cell division cycle in mammalian cells. 4 CDK1 in complex with B-type cyclins regulates the mitotic entry of the cell cycle. Once DNA damages occur, CDK1/cyclin B1 becomes inacti-vated, and cells are prevented from entering mitosis until the damages are repaired. CDK1 is inactivated by the nuclear vs. cytoplasmic kinases wee1 and Myt1, which phosphorylate CDK1 on its tyrosin-14 and-15 sites. 5 while it is activated by the antagonist of wee1 and Myt1, a family of phosphatases of Cdc25A, B and C dephosphorylate CDK1 on the same tyrosin-sites served for wee1 and Myt1. 6 The proper level and activity of CDK1 is thus kept in balance by these kinases and phosphatases that are involved in the cell cycle progression (Fig. 1). However, the role of CDK1 and the regulation of its phosphorylation and subcellular localization upon cellular response to chemo-therapeutic drugs are poorly understood. in a recent issue of Cell Cycle, Hedblom et al. 7 showed that altered level of CDK1 is associated with disease recurrence and poor overall survival of patients with acute myeloid leuke-mia. These novel findings indicate that CDK1 is a critical factor mediating cellular response to ATRA treatment. Only elimination of CDK1, not CDK2, causes a decreased proportion of G 0 / G 1 cells and a concomitant increase in mitotic cells, suggesting that cells without proper level of CDK1 had accelerated mitosis. Defects in CDK1 expression level thus confer U-937 leukemic cells to be less sensitive to all trans retinoic acid (ATRA)-induced G 0 /G 1 cell cycle arrest and differentiation. Hedblom et al. 7 demonstrate that defects in CDK1 expression cause alterations in the expression levels and activities of several proteins, which are the key regulators for cell growth and survival. These include: (1) elimination of CDK1 in U-937 cells leads to a significant reduction in the level of P27 kip , a key regulator for G …