PMID- 19914168
OWN - NLM
STAT- MEDLINE
DCOM- 20091209
LR  - 20220330
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 139
IP  - 4
DP  - 2009 Nov 13
TI  - Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and 
      TGF-beta pathways.
PG  - 757-69
LID - 10.1016/j.cell.2009.09.035 [doi]
AB  - TGF-beta and BMP receptor kinases activate Smad transcription factors by 
      C-terminal phosphorylation. We have identified a subsequent agonist-induced 
      phosphorylation that plays a central dual role in Smad transcriptional activation 
      and turnover. As receptor-activated Smads form transcriptional complexes, they 
      are phosphorylated at an interdomain linker region by CDK8 and CDK9, which are 
      components of transcriptional mediator and elongation complexes. These 
      phosphorylations promote Smad transcriptional action, which in the case of Smad1 
      is mediated by the recruitment of YAP to the phosphorylated linker sites. An 
      effector of the highly conserved Hippo organ size control pathway, YAP supports 
      Smad1-dependent transcription and is required for BMP suppression of neural 
      differentiation of mouse embryonic stem cells. The phosphorylated linker is 
      ultimately recognized by specific ubiquitin ligases, leading to 
      proteasome-mediated turnover of activated Smad proteins. Thus, nuclear CDK8/9 
      drive a cycle of Smad utilization and disposal that is an integral part of 
      canonical BMP and TGF-beta pathways.
FAU - Alarcon, Claudio
AU  - Alarcon C
AD  - Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New 
      York, NY 10021, USA.
FAU - Zaromytidou, Alexia-Ileana
AU  - Zaromytidou AI
FAU - Xi, Qiaoran
AU  - Xi Q
FAU - Gao, Sheng
AU  - Gao S
FAU - Yu, Jianzhong
AU  - Yu J
FAU - Fujisawa, Sho
AU  - Fujisawa S
FAU - Barlas, Afsar
AU  - Barlas A
FAU - Miller, Alexandria N
AU  - Miller AN
FAU - Manova-Todorova, Katia
AU  - Manova-Todorova K
FAU - Macias, Maria J
AU  - Macias MJ
FAU - Sapkota, Gopal
AU  - Sapkota G
FAU - Pan, Duojia
AU  - Pan D
FAU - Massague, Joan
AU  - Massague J
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - BFU2008-02795/PHS HHS/United States
GR  - R01 CA034610/CA/NCI NIH HHS/United States
GR  - R01 EY015708/EY/NEI NIH HHS/United States
GR  - R37 CA034610-27/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - EY015708/EY/NEI NIH HHS/United States
GR  - R37 CA034610/CA/NCI NIH HHS/United States
GR  - CA34610/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Smad Proteins)
RN  - 0 (Smad1 Protein)
RN  - 0 (Smad1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, mouse)
RN  - EC 2.7.11.22 (Cdk9 protein, mouse)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 8)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 9)
SB  - IM
CIN - Cell. 2009 Nov 13;139(4):658-60. PMID: 19914161
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Bone Morphogenetic Proteins/*metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Contact Inhibition
MH  - Cyclin-Dependent Kinase 8/*metabolism
MH  - Cyclin-Dependent Kinase 9/*metabolism
MH  - Embryo, Mammalian/cytology
MH  - Humans
MH  - Mice
MH  - Organ Size
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Structure, Tertiary
MH  - Signal Transduction
MH  - Smad Proteins/chemistry/*genetics
MH  - Smad1 Protein/genetics
MH  - *Transcriptional Activation
MH  - Transforming Growth Factor beta/*metabolism
MH  - YAP-Signaling Proteins
PMC - PMC2818353
MID - NIHMS155352
EDAT- 2009/11/17 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/11/13
CRDT- 2009/11/17 06:00
PHST- 2009/02/05 00:00 [received]
PHST- 2009/07/02 00:00 [revised]
PHST- 2009/09/23 00:00 [accepted]
PHST- 2009/11/17 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/11/13 00:00 [pmc-release]
AID - S0092-8674(09)01312-9 [pii]
AID - 10.1016/j.cell.2009.09.035 [doi]
PST - ppublish
SO  - Cell. 2009 Nov 13;139(4):757-69. doi: 10.1016/j.cell.2009.09.035.