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TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.
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.
Authors : Varelas Xaralabos , Sakuma Rui , Samavarchi-Tehrani Payman , Peerani Raheem , Rao Balaji M , Dembowy Joanna , Yaffe Michael B , Zandstra Peter W , Wrana Jeffrey L ,
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Pathways :
WP1411: Cell Division: First embryonic mitosis
WP1011: T Cell Receptor Signaling Pathway
WP1025: B Cell Receptor Signaling Pathway
WP1043: Calcium Regulation in the Cardiac Cell
WP1069: Integrin-mediated cell adhesion
WP1078: G1 to S cell cycle control
WP1083: Cell cycle
WP1130: T Cell Receptor Signaling Pathway
WP1144: B Cell Receptor Signaling Pathway
WP1159: Calcium Regulation in the Cardiac Cell
WP1185: Integrin-mediated cell adhesion
WP1195: G1 to S cell cycle control
WP1200: Cell cycle
WP1345: T Cell Receptor Signaling Pathway
WP1354: B Cell Receptor Signaling Pathway
WP1365: Calcium Regulation in the Cardiac Cell
WP1386: Integrin-mediated cell adhesion
WP1393: Cell cycle
WP1596: Iron Homeostasis
WP1775: Cell Cycle Checkpoints
WP1782: APC/C-mediated degradation of cell cycle proteins
WP179: Cell cycle
WP1792: Cell Cycle, Mitotic
WP1793: Cell junction organization
WP1794: Cell surface interactions at the vascular wall
Related Genes :
[BT3 At1g05690 F3F20.14] BTB/POZ and TAZ domain-containing protein 3 (BTB and TAZ domain protein 3)
[BT5 At4g37610 F19F18.100] BTB/POZ and TAZ domain-containing protein 5 (BTB and TAZ domain protein 5)
[BT1 At5g63160 MDC12.13] BTB/POZ and TAZ domain-containing protein 1 (BTB and TAZ domain protein 1)
[BT2 At3g48360 T29H11.120] BTB/POZ and TAZ domain-containing protein 2 (BTB and TAZ domain protein 2)
[BT4 At5g67480 K9I9.4] BTB/POZ and TAZ domain-containing protein 4 (BTB and TAZ domain protein 4)
[taz1 myb myb1 SPAC16A10.07c] Telomere length regulator taz1
[TAZ EFE2 G4.5] Tafazzin (Protein G4.5)
[WWTR1 TAZ] WW domain-containing transcription regulator protein 1 (Transcriptional coactivator with PDZ-binding motif)
[TAZ1 YPR140W] Lysophosphatidylcholine acyltransferase (EC 2.3.1.23) (1-acylglycerophosphocholine O-acyltransferase) (Tafazzin homolog) (lyso-PC acyltransferase)
[taf1 atg11 cvt9 SPAC7D4.04] Taz1-interacting factor 1 (Protein taf1) (Autophagy-related protein 11) (Cytoplasm to vacuole targeting protein 9)
[Wwtr1 Taz] WW domain-containing transcription regulator protein 1 (Transcriptional coactivator with PDZ-binding motif)
[Taz CG8766] Tafazzin homolog (dTAZ)
[ZBTB18 RP58 TAZ1 ZNF238] Zinc finger and BTB domain-containing protein 18 (58 kDa repressor protein) (Transcriptional repressor RP58) (Translin-associated zinc finger protein 1) (TAZ-1) (Zinc finger protein 238) (Zinc finger protein C2H2-171)
[ndhF] NAD(P)H-quinone oxidoreductase subunit 5, chloroplastic (EC 1.6.5.-) (NADH-plastoquinone oxidoreductase subunit 5) (Fragment)
[Taz Taz_mapped rCG_43825] Tafazzin (Tafazzin (Cardiomyopathy, dilated 3A (X-linked); endocardial fibroelastosis 2; Barth syndrome) (Mapped), isoform CRA_c)
[Dis3 dDis3 dis3 Dmel\CG6413 dRrp44 Rrp44 Taz taz CG6413 Dmel_CG6413] Dis3, isoform A (Dis3, isoform B)
[Taz RP23-436K3.6-015] Tafazzin
[cob] Cytochrome b (Fragment)
[taz DDB_G0291922] Putative lysophosphatidylcholine acyltransferase (EC 2.3.1.23) (1-acylglycerophosphocholine O-acyltransferase) (Tafazzin homolog)
[Taz] Tafazzin (Tafazzin exon 5 and exon 9 deleted variant long form)
[Taz] Tafazzin
[Taz] Tafazzin (Fragment)
[CREBBP CBP] CREB-binding protein (EC 2.3.1.48)
[Crebbp Cbp] CREB-binding protein (EC 2.3.1.48)
[EP300 P300] Histone acetyltransferase p300 (p300 HAT) (EC 2.3.1.48) (E1A-associated protein p300) (Histone butyryltransferase p300) (EC 2.3.1.-) (Histone crotonyltransferase p300) (EC 2.3.1.-) (Protein propionyltransferase p300) (EC 2.3.1.-)
[Taz mCG_129905 RP23-436K3.6-001] Tafazzin (Tafazzin exon 5 deleted variant long form) (Tafazzin, isoform CRA_e)
[Taz RP23-436K3.6-020] Tafazzin
[Crebbp Cbp] CREB-binding protein (EC 2.3.1.48)
[Ep300 P300] Histone acetyltransferase p300 (p300 HAT) (EC 2.3.1.48) (E1A-associated protein p300) (Histone butyryltransferase p300) (EC 2.3.1.-) (Histone crotonyltransferase p300) (EC 2.3.1.-) (Protein propionyltransferase p300) (EC 2.3.1.-)
[Taz] Uncharacterized protein
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