PMID- 10485843
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 17
DP  - 1999 Sep 1
TI  - The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta
      signaling.
PG  - 2196-206
AB  - Smad proteins are critical signal transducers downstream of the receptors of the 
      transforming growth factor-beta (TGFbeta) superfamily. On phosphorylation and
      activation by the active TGFbeta receptor complex, Smad2 and Smad3 form
      hetero-oligomers with Smad4 and translocate into the nucleus, where they interact
      with different cellular partners, bind to DNA, regulate transcription of various 
      downstream response genes, and cross-talk with other signaling pathways. Here we 
      show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3,
      and Smad4 on a TGFbeta-responsive promoter element and repress their abilities to
      activate transcription through recruitment of the nuclear transcriptional
      corepressor N-CoR and possibly its associated histone deacetylase complex.
      Overexpression of Ski in a TGFbeta-responsive cell line renders it resistant to
      TGFbeta-induced growth inhibition and defective in activation of JunB expression.
      This ability to overcome TGFbeta-induced growth arrest may be responsible for the
      transforming activity of Ski in human and avian cancer cells. Our studies suggest
      a new paradigm for inactivation of the Smad proteins by an oncoprotein through
      transcriptional repression.
FAU - Luo, K
AU  - Luo K
AD  - Life Sciences Division, Lawrence Berkeley National Laboratory (LBNL), Berkeley,
      California 94720 USA. k_luo@ux5.lbl.gov
FAU - Stroschein, S L
AU  - Stroschein SL
FAU - Wang, W
AU  - Wang W
FAU - Chen, D
AU  - Chen D
FAU - Martens, E
AU  - Martens E
FAU - Zhou, S
AU  - Zhou S
FAU - Zhou, Q
AU  - Zhou Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (SMAD4 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad4 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 126648-96-2 (SKI protein, human)
SB  - IM
MH  - Cell Line
MH  - DNA-Binding Proteins/*metabolism
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Lymphotoxin-alpha/*physiology
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Receptors, Transforming Growth Factor beta/*physiology
MH  - Recombinant Proteins/metabolism
MH  - Retroviridae/genetics
MH  - Signal Transduction
MH  - Smad2 Protein
MH  - Smad3 Protein
MH  - Smad4 Protein
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/metabolism
MH  - Transfection
PMC - PMC316985
EDAT- 1999/09/15 00:00
MHDA- 1999/09/15 00:01
CRDT- 1999/09/15 00:00
PHST- 1999/09/15 00:00 [pubmed]
PHST- 1999/09/15 00:01 [medline]
PHST- 1999/09/15 00:00 [entrez]
AID - 10.1101/gad.13.17.2196 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Sep 1;13(17):2196-206. doi: 10.1101/gad.13.17.2196.