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TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex

Yu Tian1, Robert Kolb, Jeong-Ho Hong

  • 1Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

Molecular and Cellular Biology
|July 20, 2007
PubMed

Insights

The transcriptional regulator TAZ binds beta-Trcp, impacting protein degradation. TAZ deficiency causes polycystic kidney disease (PKD) by increasing polycystin 2 (PC2) levels, revealing TAZ

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The transcriptional regulator TAZ has known roles in gene expression.
  • Polycystic kidney disease (PKD) is a genetic disorder characterized by kidney cyst formation.
  • Protein degradation pathways, such as ubiquitination, are crucial for cellular homeostasis.

Purpose of the Study:

  • To investigate the novel functions of the transcriptional regulator TAZ.
  • To elucidate the molecular mechanisms underlying TAZ-deficient polycystic kidney disease (PKD).
  • To explore the role of TAZ in protein degradation pathways.

Main Methods:

  • Generation and analysis of TAZ knockout (TAZ-/-) mice.
  • Investigation of polycystin 2 (PC2) expression and degradation in TAZ-/- kidneys.
  • Biochemical assays to study TAZ-beta-Trcp binding and PC2-TAZ interactions.
  • Functional studies in zebrafish models.

Main Results:

  • TAZ knockout mice develop polycystic kidney disease (PKD) and emphysema.
  • PC2 is overexpressed in TAZ-/- kidneys due to impaired degradation via the SCF(beta-Trcp) ubiquitin ligase pathway.
  • Phosphorylation-dependent TAZ-beta-Trcp interaction regulates PC2 degradation; disruption prevents degradation.
  • TAZ depletion in zebrafish also leads to cystic kidneys and PC2 overexpression.

Conclusions:

  • TAZ functions as a binding partner for the F-box protein beta-Trcp, regulating protein degradation.
  • Defects in the TAZ-mediated protein degradation pathway contribute to the pathogenesis of polycystic kidney disease (PKD).
  • This pathway is conserved across vertebrate species.

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