PMID- 26456820
OWN - NLM
STAT- MEDLINE
DCOM- 20160804
LR  - 20211203
IS  - 2211-1247 (Electronic)
VI  - 13
IP  - 3
DP  - 2015 Oct 20
TI  - Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins.
PG  - 524-532
LID - S2211-1247(15)01025-6 [pii]
LID - 10.1016/j.celrep.2015.09.014 [doi]
AB  - As the key effector in the Hippo pathway, YAP was identified as an oncoprotein 
      whose expression is elevated in various human cancers. However, the development 
      of potentially therapeutic compounds targeting YAP has been slow and limited. 
      Here, we find that tankyrase inhibitors suppress YAP activity. This effect is 
      mediated by anigomotin (AMOT) family proteins. Tankyrases associate with AMOT 
      family proteins and promote their degradation through E3 ligase RNF146. By 
      antagonizing tankyrase activity, tankyrase inhibitors stabilize AMOT family 
      proteins, thereby suppressing YAP oncogenic functions. Together, our studies not 
      only demonstrate the tankyrase-RNF146-AMOT axis as an upstream pathway regulating 
      YAP but also reveal a therapeutic opportunity in targeting YAP for cancer 
      treatment.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Wang, Wenqi
AU  - Wang W
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. 
      Electronic address: wwang5@mdanderson.org.
FAU - Li, Nan
AU  - Li N
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Li, Xu
AU  - Li X
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Tran, My Kim
AU  - Tran MK
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Han, Xin
AU  - Han X
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Chen, Junjie
AU  - Chen J
AD  - Department of Experimental Radiation Oncology, The University of Texas MD 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. 
      Electronic address: jchen8@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA092312/CA/NCI NIH HHS/United States
GR  - R01 CA100109/CA/NCI NIH HHS/United States
GR  - CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA089239/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20151008
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (AMOT protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Angiomotins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (G007-LK)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Sulfones)
RN  - 0 (Transcription Factors)
RN  - 0 (Triazoles)
RN  - 0 (XAV939)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.3.2.27 (RNF146 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.4.2.30 (Tankyrases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Angiomotins
MH  - Enzyme Inhibitors/*pharmacology
MH  - HEK293 Cells
MH  - Heterocyclic Compounds, 3-Ring/pharmacology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - MCF-7 Cells
MH  - Membrane Proteins/*metabolism
MH  - Microfilament Proteins
MH  - Phosphoproteins/*metabolism
MH  - Protein Binding
MH  - Protein Stability
MH  - *Proteolysis
MH  - Sulfones/pharmacology
MH  - Tankyrases/*antagonists & inhibitors/metabolism
MH  - Transcription Factors
MH  - Triazoles/pharmacology
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - YAP-Signaling Proteins
PMC - PMC4618173
MID - NIHMS722396
EDAT- 2015/10/13 06:00
MHDA- 2016/08/05 06:00
PMCR- 2015/10/24
CRDT- 2015/10/13 06:00
PHST- 2015/05/25 00:00 [received]
PHST- 2015/07/20 00:00 [revised]
PHST- 2015/09/03 00:00 [accepted]
PHST- 2015/10/13 06:00 [entrez]
PHST- 2015/10/13 06:00 [pubmed]
PHST- 2016/08/05 06:00 [medline]
PHST- 2015/10/24 00:00 [pmc-release]
AID - S2211-1247(15)01025-6 [pii]
AID - 10.1016/j.celrep.2015.09.014 [doi]
PST - ppublish
SO  - Cell Rep. 2015 Oct 20;13(3):524-532. doi: 10.1016/j.celrep.2015.09.014. Epub 2015 
      Oct 8.