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Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Regulated Protein Degradation

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Anaphase Promoting Complex

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Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay
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UAF1 is a subunit of multiple deubiquitinating enzyme complexes.

Martin A Cohn1, Younghoon Kee, Wilhelm Haas

  • 1Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

The Journal of Biological Chemistry
|December 17, 2008
PubMed
Summary

The UAF1 protein activates deubiquitinating enzymes USP12 and USP46, similar to its role with USP1. This suggests UAF1 may regulate a subclass of human deubiquitinating enzymes, impacting cellular processes.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Ubiquitination and deubiquitination are critical for cellular regulation.
  • Deubiquitinating enzymes (DUBs) control this balance, with specific DUBs playing key roles.
  • UAF1 protein was previously identified as an activator of USP1, a DUB involved in the Fanconi anemia pathway.

Purpose of the Study:

  • To identify novel deubiquitinating enzyme complexes.
  • To investigate the role of UAF1 in regulating other DUBs.
  • To explore the potential for UAF1 to regulate a subclass of DUBs.

Main Methods:

  • Isolation and characterization of multisubunit protein complexes.
  • Biochemical assays to determine enzymatic activity.
  • Protein complex purification and subunit identification.

Main Results:

  • Two novel deubiquitinating enzyme complexes containing USP12 and USP46 were isolated.
  • UAF1 protein was identified as a subunit in both USP12 and USP46 complexes.
  • UAF1 was shown to regulate the enzymatic activity of both USP12 and USP46 complexes.

Conclusions:

  • UAF1 protein acts as a regulatory subunit for a subclass of human deubiquitinating enzymes, including USP1, USP12, and USP46.
  • This finding suggests a broader role for UAF1 in controlling deubiquitination.
  • WD40-repeat containing proteins may generally regulate DUB activity and substrate specificity.