Nuclear hormone receptor coregulator GRIP1 suppresses, whereas SRC1A and p/CIP coactivate, by domain-specific binding

Hung-Yi Wu1, Yasuo Hamamori, Jianming Xu

  • 1Institute for Genetic Medicine and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

Insights

p160 proteins, like SRC1A and p/CIP, can activate gene expression, while GRIP1 represses it. This study reveals how these coactivators interact with transcription factors like MyoD, influencing gene regulation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Protein-Protein Interactions

Background:

  • p160 proteins were initially identified as nuclear hormone receptor coactivators.
  • Understanding the diverse roles of p160 family members in gene regulation is crucial.

Purpose of the Study:

  • To investigate the functional roles of p160 family members in transcription regulation.
  • To elucidate the mechanisms by which p160 proteins interact with transcription factors.

Main Methods:

  • Functional assays to assess gene expression.
  • Analysis of protein-protein interactions between p160 proteins and transcription factors.

Main Results:

  • p160 family members exhibit opposing roles in regulating gene expression by the same transcription factor.
  • SRC1A and p/CIP act as coactivators for MyoD, while GRIP1 functions as a repressor.
  • GRIP1 competes with other coactivators (SRC1A, p/CIP, p300) for binding sites on MyoD, suggesting a regulatory mechanism.

Conclusions:

  • p160 coactivators can have opposing functions, acting as either coactivators or corepressors.
  • Differential binding of p160 proteins to transcription factor activation domains regulates gene expression.
  • Competition for binding sites on transcription factors is a key mechanism controlling their activity.

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