Affordable Access

Regulation of the WW domain-containing transcriptional coactivator TAZ by multisite phosphorylation

McGill University
Publication Date
  • Biology - Molecular
  • Biology
  • Medicine


A WW domain containing transcriptional coactivator, TAZ (transcriptional coactivator with PDZ-binding motif) plays an important role in transcriptional regulation and perhaps tumorigenesis. Recent studies of TAZ knockout mice reveal a novel function of TAZ in kidney development, polycystic kidney disease, and pulmonary emphysema. As a binding partner of the F-box protein β-TRCP, TAZ regulates kidney homeostasis. It has been shown that as a transcriptional coactivator, TAZ is modulated by the Hippo pathway through phosphorylation and 14-3-3 binding. However, the regulatory mechanism of TAZ interaction with β-TRCP is not well understood. To gain insights into this regulation and the functional consequences, I sought to study the phosphorylation of TAZ and elucidate how it regulates the β-TRCP binding. From this work, I discover that a key component of the Hippo pathway, the large tumor suppressor kinase 2 (LATS2), as well as cAMP-dependent protein kinase (also known as protein kinase A or PKA), phosphorylates TAZ at serine 306 and promotes β-TRCP2 binding. This finding not only poses a novel post-translational modification model for TAZ, but also suggests a new function of the Hippo pathway in kidney homeostasis.

There are no comments yet on this publication. Be the first to share your thoughts.