Pattern of protein synthesis in monkey cells infected by simian virus 40

Journal ArticleAfter infection of several permanent monkey cell lines by simian virus 40 (SV40), four additional protein bands can be detected by simple sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell extracts. These bands appear only after the onset of viral deoxyribonucleic acid (DNA) synthesis, and inhibitors of DNA synthesis prevent their appearance. Three of them correspond to three previously identified capsid components, VP1, VP2, and VP3. The fourth protein band, which does not correspond to a previously identified virion component, is induced by SV40 infection of CV-1 and BSC-1 cultures but not by infection of MA-134 cultures

Origin and destiny of adenovirus proteins

Journal ArticleLytic infection of human cells by adenovirus proceeds by a temporal expression of genes. Classically two phases have been defined: an early phase, which includes events occurring before the onset of DNA synthesis (8 hours), and a late phase, including events whose existence depends on the onset of DNA synthesis. During the late phase of infection, host cell macromolecular synthesis is progressively inhibited so that eventuallly only virus-specfic macromolecules are synthesized

Key Equations in the Tuljapurkar-Lee Model of the Social Security System

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Damage-mediated phosphorylation of human p53 threonine 18 through a cascade mediated by a casein 1-like kinase: effect on Mdm2 binding

The p53 tumor suppressor protein is stabilized in response to ionizing radiation and accumulates in the nucleus. Stabilization is thought to involve disruption of the interaction between the p53 protein and Mdm2, which targets p53 for degradation. Here we show that the direct association between a p53 N-terminal peptide and Mdm2 is disrupted by phosphorylation of the peptide on Thr18 but not by phosphorylation at other N-terminal sites, including Ser15 and Ser37. Thr18 was phosphorylated in vitro by casein kinase (CK1); this process required the prior phosphorylation of Ser15. Thr18 was phosphorylated in vivo in response to DNA damage, and such phosphorylation required Ser15. Our results suggest that stabilization of p53 after ionizing radiation may result, in part, from an inhibition of Mdm2 binding through a phosphorylation-phosphorylation cascade involving DNA damage-activated phosphorylation of p53 Ser15 followed by phosphorylation of Thr18

Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5′ untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5′ UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels