PMID- 18568018
OWN - NLM
STAT- MEDLINE
DCOM- 20080804
LR  - 20211203
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Linking)
VI  - 10
IP  - 7
DP  - 2008 Jul
TI  - TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic 
      stem-cell self-renewal.
PG  - 837-48
LID - 10.1038/ncb1748 [doi]
AB  - Transforming growth factor-beta (TGFbeta) family members regulate many 
      developmental and pathological events through Smad transcriptional modulators. 
      How nuclear accumulation of Smad is coupled to the transcriptional machinery is 
      poorly understood. Here we demonstrate that in response to TGFbeta stimulation 
      the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is 
      recruited to TGFbeta response elements. In human embryonic stem cells TAZ is 
      required to maintain self-renewal markers and loss of TAZ leads to inhibition of 
      TGFbeta signalling and differentiation into a neuroectoderm lineage. In the 
      absence of TAZ, Smad2/3-4 complexes fail to accumulate in the nucleus and 
      activate transcription. Furthermore, TAZ, which itself engages in shuttling, 
      dominantly controls Smad nucleocytoplasmic localization and can be retained in 
      the nucleus by transcriptional co-factors such as ARC105, a component of the 
      Mediator complex. TAZ thus defines a hierarchical system regulating Smad nuclear 
      accumulation and coupling to the transcriptional machinery.
FAU - Varelas, Xaralabos
AU  - Varelas X
AD  - Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, 
      Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
FAU - Sakuma, Rui
AU  - Sakuma R
FAU - Samavarchi-Tehrani, Payman
AU  - Samavarchi-Tehrani P
FAU - Peerani, Raheem
AU  - Peerani R
FAU - Rao, Balaji M
AU  - Rao BM
FAU - Dembowy, Joanna
AU  - Dembowy J
FAU - Yaffe, Michael B
AU  - Yaffe MB
FAU - Zandstra, Peter W
AU  - Zandstra PW
FAU - Wrana, Jeffrey L
AU  - Wrana JL
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080622
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (MED15 protein, human)
RN  - 0 (Mediator Complex)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad4 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (TAFAZZIN protein, human)
SB  - IM
MH  - Active Transport, Cell Nucleus/*physiology
MH  - Acyltransferases
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Embryonic Stem Cells/cytology/*physiology
MH  - Genes, Reporter
MH  - Humans
MH  - Mediator Complex
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction/physiology
MH  - Smad2 Protein/genetics/*metabolism
MH  - Smad3 Protein/genetics/*metabolism
MH  - Smad4 Protein/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2008/06/24 09:00
MHDA- 2008/08/05 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/03/10 00:00 [received]
PHST- 2008/05/19 00:00 [accepted]
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/08/05 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - ncb1748 [pii]
AID - 10.1038/ncb1748 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2008 Jul;10(7):837-48. doi: 10.1038/ncb1748. Epub 2008 Jun 22.