Regulation of tankyrase activity by a catalytic domain dimer interface

Chen Fan, Nageswari Yarravarapu, Hua Chen, Ozlem Kulak, Pranathi Dasari, Jeremiah Herbert, Kiyoshi Yamaguchi, Lawrence Lum, Xuewu Zhang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Tankyrases (TNKS and TNKS2) are enzymes that catalyze poly-ADP-ribosylation (PARsylation) of their target proteins. Tankyrase-mediated PARsylation plays critical regulatory roles in cell signaling, particularly in the Wnt/β-catenin pathway. The sterile alpha motif (SAM) domain in tankyrases mediates their oligomerization, which is essential for tankyrase function. The oligomerization regulates the catalytic activity of tankyrases, but the underlying mechanism is unclear. Our analyses of crystal structures of the tankyrase catalytic domain suggest that formation of a head-to-head dimer regulates the catalytic activity. Our activity assays show that residues in the catalytic domain dimer interface are important for the PARsylation activity of tankyrases both in solution and cells. The dimer is weak and may only form in the context of the SAM domain-mediated oligomers of tankyrases, consistent with the dependence of the tankyrase activity on the SAM domain.

Original languageEnglish (US)
JournalBiochemical and Biophysical Research Communications
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Tankyrases
Dimers
Catalytic Domain
Adenosine Diphosphate
Oligomerization
Catalyst activity
Cell signaling
Catenins
Wnt Signaling Pathway
Oligomers
Assays

Keywords

  • Dimerization
  • Oligomerization
  • PARsylation
  • Tankyrase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Regulation of tankyrase activity by a catalytic domain dimer interface. / Fan, Chen; Yarravarapu, Nageswari; Chen, Hua; Kulak, Ozlem; Dasari, Pranathi; Herbert, Jeremiah; Yamaguchi, Kiyoshi; Lum, Lawrence; Zhang, Xuewu.

In: Biochemical and Biophysical Research Communications, 01.01.2018.

Research output: Contribution to journalArticle

Fan, Chen ; Yarravarapu, Nageswari ; Chen, Hua ; Kulak, Ozlem ; Dasari, Pranathi ; Herbert, Jeremiah ; Yamaguchi, Kiyoshi ; Lum, Lawrence ; Zhang, Xuewu. / Regulation of tankyrase activity by a catalytic domain dimer interface. In: Biochemical and Biophysical Research Communications. 2018.
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AU - Yarravarapu, Nageswari

AU - Chen, Hua

AU - Kulak, Ozlem

AU - Dasari, Pranathi

AU - Herbert, Jeremiah

AU - Yamaguchi, Kiyoshi

AU - Lum, Lawrence

AU - Zhang, Xuewu

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