SELENODEIODINASE PROCESSING BY THE PROTEASOME SYSTEM

  • Bianco, Antonio, (PI)
  • Larsen, Philip Reed (PI)

Project: Research project

Description

DESCRIPTION: This is a new proposal to determine the mechanisms regulating the rate-limiting steps in the ubiquitin proteasome system leading to the controlled degradation of the Types 1, 2 and 3 selenodeiodinases. D2 is a critical enzyme regulating the first step in thyroid hormone action, the conversion of the prohormone T4 to the active hormone, T3. This process occurs intracellularly in brain, pituitary and brown fat in which the T3 produced constitutes a major fraction of the nuclear receptor-bound hormone. Furthermore, it appears that, in humans, unlike in adult rodents, D2 may also generate a significant fraction of plasma T3 by virtue of its wide tissue expression in skeletal muscle. It has been known for a number of years that post-translational regulation of D2 by substrate is a major regulatory step in determining the tissue level of the active enzyme. Recent studies have shown that degradation of D2 occurs in proteasomes, that its half-life is quite short (
StatusFinished
Effective start/end date2/1/014/30/14

Funding

  • National Institutes of Health: $279,890.00
  • National Institutes of Health: $311,326.00
  • National Institutes of Health: $305,076.00
  • National Institutes of Health: $357,080.00
  • National Institutes of Health: $122,609.00
  • National Institutes of Health: $346,725.00
  • National Institutes of Health: $328,950.00
  • National Institutes of Health: $323,200.00
  • National Institutes of Health: $346,838.00
  • National Institutes of Health: $365,672.00

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Ubiquitination
Proteasome Endopeptidase Complex
Thyroid Hormones
Hormones
gamma-Glutamyl Hydrolase
Endoplasmic Reticulum-Associated Degradation
Ubiquitin
Iodide Peroxidase
Two-Hybrid System Techniques
Brown Adipose Tissue
Triiodothyronine
Enzymes
Catalysis
Thyroxine
Endoplasmic Reticulum
Ligases
Membrane Proteins
Homeostasis
Ubiquitin-Protein Ligases
Peptides

ASJC

  • Medicine(all)