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The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.
F D Coffman, and
K L Fresa, and
S Cohen
April 1974,
Nature,
F D Coffman, and
K L Fresa, and
S Cohen
December 1977,
Nature,
F D Coffman, and
K L Fresa, and
S Cohen
September 1971,
Science (New York, N.Y.),
F D Coffman, and
K L Fresa, and
S Cohen
January 1969,
Annual review of biochemistry,
F D Coffman, and
K L Fresa, and
S Cohen
January 1978,
Current topics in microbiology and immunology,
F D Coffman, and
K L Fresa, and
S Cohen
January 1973,
Basic life sciences,
F D Coffman, and
K L Fresa, and
S Cohen
January 1997,
Indian journal of biochemistry & biophysics,
F D Coffman, and
K L Fresa, and
S Cohen
February 1979,
Cancer research,
F D Coffman, and
K L Fresa, and
S Cohen
May 1977,
Proceedings of the National Academy of Sciences of the United States of America,
F D Coffman, and
K L Fresa, and
S Cohen
January 1981,
Molecular & general genetics : MGG,
