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C Norbury

Publications and source records attributed to C Norbury.

25 records · Page 2Linked to original sources
PubMed1991

Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.

The p34cdc2 protein kinase is a conserved regulator of the eukaryotic cell cycle. Here we show that residues Thr14 and Tyr15 of mouse p34cdc2 become phosphorylated as mouse fibroblasts proceed through the cell cycle. We have mutated these residues and measured protein kinase activity of the p34cdc2 variants in a Xenopus egg extract. Phosphorylation of residues 14 and 15, which lie within the presumptive ATP-binding region of p34cdc2, normally restrains the protein kinase until it is specifically dephosphorylated and activated at the G2/M transition. Regulation by dephosphorylation of Tyr15 is conserved from fission yeast to mammals, while an extra level of regulation of mammalian p34cdc2 involves Thr14 dephosphorylation. In the absence of phosphorylation on these two residues, the kinase still requires cyclin B protein for its activation. Inhibition of DNA synthesis inhibits activation of wild-type p34cdc2 in the Xenopus system, but a mutant which cannot be phosphorylated at residues 14 and 15 escapes this inhibition, suggesting that these phosphorylation events form part of the pathway linking completion of DNA replication to initiation of mitosis.

3T3 Cells↗
PubMed1990

Controls of cell proliferation in yeast and animals.

Genetic studies using fission yeast (Schizosaccharomyces pombe) have identified a gene, cdc2, whose product (p34cdc2) is a protein kinase required for traversal of both the G1 and G2 cell cycle control points. Genetic complementation has been used to demonstrate that p34cdc2 homologues are functionally and structurally conserved in distantly related eukaryotes, and p34cdc2-related proteins are components of both maturation-promoting factor (MPF) and the M phase (growth-associated) histone H1 kinase. The p34cdc2 homologues of multicellular eukaryotes undergo potentially regulatory phosphorylation changes through the cell cycle. Phosphorylation on serine during late G1 is accompanied by a significant increase in p34cdc2 kinase activity which, by analogy with fission yeast, may betray a function related to control over entry into S phase. Phosphorylation on threonine and tyrosine in G2 precedes dephosphorylation of these residues during kinase hyperactivation and entry into mitosis. In addition, long-term control of expression of mammalian p34cdc2 homologues is likely to be exerted at the transcriptional level. These observations provide the framework of a universal model for the control of eukaryotic cell proliferation, in which the p34cdc2 protein kinase integrates multiple cues to signal the initiation of S phase and, subsequently, mitosis.

Animals↗
PubMed1988

Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.

In the fission yeast S. pombe, the Mr = 34 kd product of the cdc2+ gene (p34cdc2) is a protein kinase that controls entry into mitosis. In Xenopus oocytes and other cells, maturation-promoting factor (MPF) appears in late G2 phase and is able to cause entry into mitosis. Purified MPF consists of two major proteins of Mr approximately equal to 32 kd and 45 kd and expresses protein kinase activity. We report here that antibodies to S. pombe p34cdc2 are able to immunoblot and immunoprecipitate the approximately equal to 32 kd component of MPF from Xenopus eggs. The Mr approximately equal to 32 kd and 45 kd proteins exist as a complex that expresses protein kinase activity. These findings indicate that a Xenopus p34cdc2 homolog is present in purified MPF and suggest that p34cdc2 is a component of the control mechanism initiating mitosis generally in eukaryotic cells.

Animals↗
PubMed1986

Gene activation properties of a mouse DNA sequence isolated by expression selection.

The MES-1 element was previously isolated from restricted total mouse cellular DNA by "expression selection"--the ability to reactivate expression of a test gene devoid of its 5' enhancer sequences. Mes-1 has been tested in long-term transformation and short-term CAT expression assays. In both assays MES-1 is active independent of orientation and at a distance when placed 5' to the test gene. The element is active with heterologous promoters and functions efficiently in both rat and mouse cells. MES-1 activates expression by increasing transcription from the test gene's own start (cap) site. Thus the expression selection technique can be used for the isolation of DNA sequences with enhancer-like properties from total cellular DNA.

Acetyltransferases↗
PubMed1974

Immunity to murine sarcoma virus induced tumours. 3. Analysis of the cell populations involved in protection from lethal tumour progression of sublethally irradiated, MSV inoculated, mice.

A comparison was made between the cells responsible for demonstrable activity against MSV antigens, using both in vivo and in vitro assays. Similar cells (in terms of size and sensitivity to anti-theta serum) were detected in both assays. However, while lymphoid cells from animals at all stages post-MSV infection were active in protecting irradiated mice from the lethal effect of induction of MSV sarcomata, cells from animals at early stages post-MSV infection (when the tumour was in a progressive phase of growth) were not active in the in vitro assay. By manipulation of the in vivo assay conditions a situation was observed in which cells from "progressor animals" were able to suppress both the in vitro and in vivo activity of regressor lymphoid cells. The potential physiological role of this cell type is disussed.

Animals↗