PMID- 10535941
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - SnoN and Ski protooncoproteins are rapidly degraded in response to transforming
      growth factor beta signaling.
PG  - 12442-7
AB  - Transforming growth factor beta (TGF-beta) regulates a variety of physiologic
      processes, including growth inhibition, differentiation, and induction of
      apoptosis. Some TGF-beta-initiated signals are conveyed through Smad3; TGF-beta
      binding to its receptors induces phosphorylation of Smad3, which then migrates to
      the nucleus where it functions as a transcription factor. We describe here the
      association of Smad3 with the nuclear protooncogene protein SnoN. Overexpression 
      of SnoN represses transcriptional activation by Smad3. Activation of TGF-beta
      signaling leads to rapid degradation of SnoN and, to a lesser extent, of the
      related Ski protein, and this degradation is likely mediated by cellular
      proteasomes. These results demonstrate the existence of a cascade of the TGF-beta
      signaling pathway, which, upon TGF-beta stimulation, leads to the destruction of 
      protooncoproteins that antagonize the activation of the TGF-beta signaling.
FAU - Sun, Y
AU  - Sun Y
AD  - Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA
      02142, USA.
FAU - Liu, X
AU  - Liu X
FAU - Ng-Eaton, E
AU  - Ng-Eaton E
FAU - Lodish, H F
AU  - Lodish HF
FAU - Weinberg, R A
AU  - Weinberg RA
LA  - eng
GR  - R01CA63260/CA/NCI NIH HHS/United States
GR  - R35CA39826/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SKIL protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad3 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 126648-96-2 (SKI protein, human)
SB  - IM
MH  - Cell Line
MH  - DNA-Binding Proteins/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Plasminogen Activator Inhibitor 1/genetics
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - *Signal Transduction
MH  - Smad3 Protein
MH  - Trans-Activators/metabolism
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/*metabolism
PMC - PMC22943
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12442 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12442-7. doi:
      10.1073/pnas.96.22.12442.