Increased secretion of adrenal cortical steroids may account in part for its cancer inhibitory activity of energy restriction (ER). To test this hypothesis, a study was conducted to determine the effects of dietary administration of corticosterone on the post-initiation stage of mammary carcinogenesis. Eighty-four female Sprague-Dawley rats were injected with 50 mg 1-methyl-1-nitrosourea/kg bod...

Traditionally, well-defined three-dimensional structure has been thought to be essential for protein function. However, myriad biological functions are performed by highly dynamic, intrinsically disordered proteins (IDPs). IDPs often fold upon binding their biological targets and frequently show 'binding diversity' by targeting multiple ligands. We sought to understand the physical basis of IDP...

A constitutively active form of mitogen-activated protein kinase kinase (MEK1) was synthesized under control of a zinc-inducible promoter in NIH 3T3 fibroblasts. Zinc treatment of serum-starved cells activated extracellular signal-regulated protein kinases (ERKs) and induced expression of cyclin D1. Newly synthesized cyclin D1 assembled with cyclin-dependent kinase-4 (CDK4) to form holoenzyme c...

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In addition to their well-established roles at the G1-S checkpoint, recent reports support a role for universal cyclin-dependent kinase (CDK) inhibitors in the control of G2-M and suggest that their induction may stimulate the occurrence of endomitosis or polyploidy in a number of physiological settings. In this report, the stable expression of the p120E4F transcription factor, which attenuates...

The eukaryotic cell cycle is characterized by alternating oscillations in the activities of cyclin-dependent kinase (Cdk) and the anaphase-promoting complex (APC). Successful completion of the cell cycle is dependent on the precise, temporally ordered appearance of these activities. A modest level of Cdk activity is sufficient to initiate DNA replication, but mitosis and APC activation require ...

Cyclin-dependent kinase 5 (cdk5) is found in an active form only in neuronal cells. Activation by virtue of association with the cyclin-like neuronal proteins p35 (or its truncated form p25) and p39 is the only mechanism currently shown to regulate cdk5 catalytic activity. In addition to cyclin binding, other members of the cdk family require for maximal activation phosphorylation of a Ser/Thr ...

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyroid adenoma, breast cancer, colon cancer, lymphoma, melanoma, and prostate canc...

Wee1 kinases regulate the cell cycle through inhibitory phosphorylation of cyclin-dependent kinases (CDKs). Eukaryotic cells express multiple CDKs, each having a kinase subunit (Cdk) and a regulatory "cyclin" subunit that function at different stages of the cell cycle to regulate distinct processes. The cyclin imparts specificity to CDK-substrate interactions and also determines whether a parti...

Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232. Mutations in these kinases have op...