CRYPTIC PROTEASE GENES AND THE TRIGGERS FOR CELL DEATH

Project Details

Description

DESCRIPTION (adapted from investigator's abstract): As large amounts of
sequence information become available from the Human Genome Project,
sequence analyses will provide clearer evidence that numerous human diseases
or disorders have deep evolutionary roots. The proposed research addresses
the evolutionary origins of proteases and cell death responses as a case in
point. Specifically, the proposed research seeks to: (1) examine the
evolutionary origins of autocatalyzed cell death associated with the stress
induced expression of novel (cryptic) proteases in single-celled, asexual
eucaryotes, specifically the obligate photoautotrophic chlorophyte alga,
Dunaliella tertiolecta, (2) elucidate the molecular triggers in
physiological stress responses that lead to the induction of novel proteases
and catastrophic cell death in such cells, and (3) examine to what extent
the cryptic proteases are ubiquitous in eucaryotes. These goals address the
biological significance of apoptosis and autocatalyzed cell death in the
context of the evolution of somatic eucaryotes and the processes that
repress or silence the expression of cryptic proteases encoded within their
nuclear genomes. In humans, protease-triggered apoptosis occurs in
cytotoxic T lymphocytes and other defensive cell lines, but is also a
symptom of numerous chronic diseases or disorders with little or no clear
Mendelian genetic lineage. It is hypothesize that the genes encoding the
stress-induced proteases have been incorporated into bacterial and
eukaryotic genomes from relic viral infections, comparable to the endogenous
retroviral protease genes found in metazoans. These genes, normally
silenced either by repressor factors or transpositions, appear to be
derepressed when the organism is selectively stressed.
StatusFinished
Effective start/end date9/30/988/31/00

Funding

  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences

ASJC

  • Genetics
  • Molecular Biology
  • Cell Biology

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