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PMID: 7937793 Published · ppublish English Journal Article

Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 20 ·1994-09-27 ·Pages 9480-4

O'Connor PM, Ferris DK, Hoffmann I, Jackman J, Draetta G, Kohn KW

Abstract

G2 arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes. We investigated the possibility that this might be due to a suppression of cdc25C phosphatase activity. cdc25C from interphase cells migrated as a 54- to 57-kDa doublet in SDS gels and exhibited basal phosphatase activity. cdc25C from mitotic cells migrated as a 66-kDa hyperphosphorylated species and exhibited elevated phosphatase activity. cdc25C hyperphosphorylation and activation were mediated by cdc2, supporting the view of a cdc2-cdc25C autocatalytic feedback loop. Immunofluorescence and cell fractionation studies suggested cdc2-cdc25C interaction occurred within the cytoplasm. Cells arrested in G2 phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species. Our findings suggest that checkpoints guarding against mitotic entry in the presence of unreplicated or damaged DNA suppress formation of the cdc2-cdc25C autocatalytic feedback loop that normally brings about rapid activation of cdc2.

MeSH Terms
Aphidicolin/pharmacology Burkitt Lymphoma CDC2 Protein Kinase/metabolism Cell Cycle Proteins Cell Line G2 Phase/drug effects,physiology HeLa Cells Humans Interphase Kinetics Mechlorethamine/pharmacology Nocodazole/pharmacology Proteins/metabolism Time Factors Tumor Cells, Cultured cdc25 Phosphatases
Chemicals
Cell Cycle Proteins Proteins Aphidicolin Mechlorethamine CDC2 Protein Kinase CDC25C protein, human cdc25 Phosphatases Nocodazole
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
O'Connor P M
Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Ferris D K
Hoffmann I
Jackman J
Draetta G
Kohn K W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.20.9480
Published
1994-09-27
Pages
9480-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44836
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.20.9480 PMC Full Text View journal details
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