REGULATION OF NEUROPEPTIDE-PROCESSING ENZYMES

Project: Research project

Project Details

Description

This is an application for an ADAMHA RSDA level II.

The applicant has a long-standing interest in the regulation of opioid
peptides, as well as other peptide neurotransmitters; this regulation may
be important in understanding the molecular basis of drug abuse. The
candidate's immediate career goals involve investigations of various
neuropeptide-processing enzymes, such as carboxypeptidase E (CPE), a
dynorphin-processing endopeptidase, and other enzymes. A key issue
concerns the regulation of various enzymes, and the implications for
neuropeptide production. Long-term career goals involve applying the
information from studies on the regulation of enzymes towards the in vivo
regulation that may occur upon drug addiction.

The RSDA award will enhance the research activities of the applicant by
freeing him of the responsibilities of managing the Medical Pharmacology
course. The applicant, currently a co-organizer of the course, would be
relieved of these obligations if the award is made. Also, other
administrative and teaching duties would be reduced so that >80% effort
could be directed towards research.

The environment at Albert Einstein College is highly supportive, with
many active research groups studying related topics: signal transduction
mechanisms, neurotransmitter receptors, gene regulation, protein
structure and function, and more.

The research plan is focused on the regulation of CPE, an essential
enzyme in the production of opioid and other peptide neurotransmitters.
The overall objective of these studies is to examine the mechanisms by
which CPE is regulated. In cell culture systems, various treatments will
be examined for an effect on the levels of CPE mRNA and enzymatic
activity. Various soluble and membrane-bound forms of CPE will be
examined; since membrane-bound CPE is less active than the soluble forms,
this may represent an important step for enzyme regulation. The post-
translational modification responsible for the differences between
various forms of CPE will be determined, and the enzymes that process CPE
will be identified. The structure-function relationship of CPE will be
examined using a variety of techniques with native and mutant forms of
CPE. The CPE gene will also be studied, with the focus on understanding
the regulatory elements that give rise to the tissue-specific and
pharmacologically-induced regulation of CPE mRNA. In addition to these
studies on CPE, the co-regulation of CPE and other peptide processing
enzymes (prohormone convertases, amidating enzymes) will also be
examined. The results of these studies will provide a better
understanding of the mechanisms for the regulation of CPE and other
neuropeptide-processing enzymes.
StatusFinished
Effective start/end date4/1/933/31/94

Funding

  • NATIONAL INSTITUTE ON DRUG ABUSE

ASJC

  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Structural Biology
  • Biochemistry
  • Pharmacology

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