TSG101 protein steady-state level is regulated posttranslationally by an evolutionarily conserved COOH-terminal
1Department of Genetics, Stanford University School of Medicine, California 94305, USA.
Cancer Research
|April 5, 2000
Summary
Tumor susceptibility gene 101 (TSG101) levels outside a narrow range cause abnormal cell growth. TSG101 protein degradation regulates its steady-state level, preventing neoplastic transformation.
Area of Science:
- Molecular biology
- Cancer research
- Cell biology
Background:
- TSG101 gene inactivation causes neoplastic transformation and tumorigenesis.
- Both TSG101 deficiency and overexpression lead to abnormal cell growth and cell cycle perturbation.
- Maintaining TSG101 within a narrow range is crucial for normal cell function.
Purpose of the Study:
- To investigate the posttranslational regulation of TSG101 protein levels.
- To identify the mechanism controlling TSG101 steady-state levels.
- To understand the role of TSG101 autoregulation in preventing abnormal cell growth.
Main Methods:
- Studied TSG101 protein degradation in cultured murine and human cells.
- Utilized chromosomally inserted adventitious constructs for TSG101 overproduction.
- Employed deletion mutants to map the autoregulation region of TSG101.
Main Results:
- TSG101 protein is maintained at a constant steady-state level via posttranslational degradation.
- Sustained TSG101 overproduction triggers compensatory down-regulation of endogenous TSG101.
- A conserved "steadiness box" near the COOH-terminal end of TSG101 is responsible for autoregulation.
Conclusions:
- TSG101 autoregulation, likely through a feedback loop involving proteolysis, maintains its precise cellular concentration.
- Dysregulation of TSG101 levels outside a narrow range contributes to neoplastic transformation.
- Understanding TSG101 regulation offers insights into cancer development and potential therapeutic targets.
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