Tankyrase, also known as tankyrase 1, is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''TNKS''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
It inhibits the binding of
TERF1
Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the ''TERF1'' gene.
Gene
The human TERF1 gene is located in the chromosome 8 at 73,921,097-73,960,357 bp. Two transcripts of this gene are alternatively spliced prod ...
to
telomeric DNA.
Tankyrase attracts substantial interest in cancer research through its interaction with
AXIN1 and
AXIN2
Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the ''AXIN2'' gene.
Function
The Axin-related protein, Axin2, presumably plays an important role in the ...
, which are negative regulators of pro-oncogenic
β-catenin
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...
signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and thus such inhibitors are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers.
Description
Tankyrase-1 is a poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-
ADP-ribosylation
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis ...
(PARylation) of
AXIN1 and
AXIN2
Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the ''AXIN2'' gene.
Function
The Axin-related protein, Axin2, presumably plays an important role in the ...
, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by
RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of
BLZF1 and
CASC3, followed by recruitment of
RNF146 and subsequent ubiquitination. Mediates PARsylation of
TERF1
Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the ''TERF1'' gene.
Gene
The human TERF1 gene is located in the chromosome 8 at 73,921,097-73,960,357 bp. Two transcripts of this gene are alternatively spliced prod ...
, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of
HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of
SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of
NUMA1. Stimulates 26S proteasome activity.
Protein interactions
TNKS has been shown to
interact with:
*
FNBP1,
*
MCL1,
*
TERF1
Telomeric repeat-binding factor 1 is a protein that in humans is encoded by the ''TERF1'' gene.
Gene
The human TERF1 gene is located in the chromosome 8 at 73,921,097-73,960,357 bp. Two transcripts of this gene are alternatively spliced prod ...
,
and
* TNKS1BP1.
References
Further reading
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{{Refend
Telomere-related proteins
Aging-related enzymes