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Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis

S E Salghetti1, M Muratani, H Wijnen

  • 1Cold Spring Harbor Laboratory, 1 Bungtown Road, P.O. Box 100, Cold Spring Harbor, NY 11724, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 8, 2000
PubMed

Insights

Many unstable transcription factors, crucial for cell growth, are degraded via ubiquitin-mediated proteolysis. Their protein destruction signals often overlap with transcription activation domains, suggesting degradation may be linked to their function.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Many transcription factors controlling cell growth are unstable proteins.
  • These proteins are degraded through ubiquitin-mediated proteolysis.
  • Previous studies on Myc showed overlap between its destruction signal and transcription activation region.

Purpose of the Study:

  • To investigate if the overlap between transcription activation and protein destruction is a general phenomenon.
  • To explore the relationship between activation domains and destruction elements in unstable transcription factors.

Main Methods:

  • Studied sequences targeting the transcription factor Myc for destruction.
  • Examined other unstable transcription factors for similar overlaps.
  • Assessed the correlation between acidic activation domain function and proteolysis signaling.
  • Tethered destruction elements from yeast cyclins to a DNA-binding domain.

Main Results:

  • A similar overlap of activation domains and destruction elements was found in other unstable transcription factors.
  • A strong correlation exists between an acidic activation domain's ability to activate transcription and signal proteolysis.
  • Destruction elements from yeast cyclins, when tethered, could activate transcription.

Conclusions:

  • The overlap of activation domains and destruction elements is a general phenomenon, not unique to Myc.
  • There is an unexpected convergence between transcription activation and protein degradation pathways.
  • Transcription factors may be destroyed as a consequence of their transcriptional activation function.

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