FUNCTION OF THE INTERFERON-INDUCED PROTEIN KINASE DAI

  • Mathews, Michael (PI)
  • MATHEWS, MICHAEL (PI)
  • MATHEWS, MICHAEL B. (PI)
  • MATHEWS, MICHAEL (PI)

Project Details

Description

DESCRIPTION (Adapted from the Investigator's Abstract):Protein kinases
play key roles in the cellular regulatory circuits of higher organisms.
The protein kinase DAI, the double-stranded RNA (dsRNA) activated
inhibitor of translation (also known as P1 or p68 kinase), is present
in most cells at a basal level. The synthesis of DAI is induced by
interferon, and kinase is activated by dsRNA in a process that involves
autophosphorylation. DAI phosphorylates the initiation factor elF-2
(eukaryotic initiation factor 2), thereby impairing the initiation of
protein synthesis; it also phosphorylates other substrates, at least in
vitro. Its role in the interferon-induced anti- viral response is well
established, and DAI has recently been implicated in malignant
transformation as well as other regulatory processes.

The objective of the research proposed here is to understand the
biological functions and biochemical activities of DAI at the molecular
level. To this end, the aims of the application are (i) to characterize
the interaction between DAI and its activator, dsRNA; (ii) to explore
the nature of its substrates and their phosphorylation by activated DAI;
(iii) to elucidate the mechanism of autophosphorylation and activation
of the enzyme; (iv) to study the biological roles of DAI, especially in
virus infection and cellular transformation; and (v) to determine the
enzyme's structure in detail using biophysical methods. In the long
term, these studies will illuminate the processes of growth control and
of virus infection, and may lead to strategies for intervention in
cancer and viral diseases.
StatusFinished
Effective start/end date9/30/936/30/10

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Molecular Biology
  • Biochemistry
  • Virology
  • Cell Biology

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