Search results for TNKS2

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Species

Types

Compartments

Reaction types

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Protein (1 results from a total of 1)

Identifier: R-HSA-3640824
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: TNKS2: Q9H2K2

Reaction (2 results from a total of 2)

Identifier: R-HSA-8948800
Species: Homo sapiens
Compartment: cytosol
PTEN can bind tankyrases TNKS (TNKS1) and TNKS2. The interaction involves the tankyrase binding motif at the N-terminus of PTEN (RYQEDG). TNKS and TNKS2 poly-ADP-ribosylate (PARylate) PTEN on glutamic acid residues E40 and E150 and on aspartic acid residue D326. PTEN PARylation is a pre-requisite for RNF146-mediated ubiquitination of PTEN (Li et al. 2015).
Identifier: R-HSA-3640858
Species: Homo sapiens
Compartment: cytosol
TNKS1 and 2 function redundantly to control AXIN protein levels through the addition of poly-ADP-ribosyl groups (PARSylation), which may lead to subsequent ubiquitination and degradation by the proteasome. In HEK293, SW480 and breast cancer cell lines, depletion of TNKS1 and 2 increases the protein levels of AXIN1 and AXIN2 resulting in increased beta-catenin phosphorylation, decreased beta-catenin abundance and decreased expression of WNT targets and WNT-responsive reporters (Huang et al, 2009; Callow et al, 2011; Waaler et al, 2012; Bao et al, 2012). In vitro, TNKS2 catalyzes the addition of ADP-ribosyl groups to the TBD fragment of AXIN1, while in vivo, both exogenous GST-AXIN1 and endogenous AXIN1 are PARSylated in a TNKS-dependent manner (Huang et al, 2009; Callow et al, 2011; Zhang et al, 2011). PARSylation is likely required for the subsequent proteasome-mediated degradation of AXIN, as the increase in levels of polyubiquitinated AXIN1 and 2 seen upon treatment of cells with the proteasome inhibitor MG132 is lost if cells are simultaneously treated with an inhibitor of TNKS1 and 2 (Huang et al, 2009). Although in this reaction, TNKS is shown PARSylating unbound AXIN, it is likely that this regulation occurs at the level of the destruction complex. Also not shown in this reaction is the ability of TNKS to catalyze autoPARSylation reactions, which ultimately lead to its own degradation (Yeh et al, 2006; Huang et al, 2009; Zhang et al, 2011).
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