PMID- 10587642
OWN - NLM
STAT- MEDLINE
DCOM- 20000908
LR  - 20061115
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 1
IP  - 8
DP  - 1999 Dec
TI  - Ubiquitin-dependent degradation of TGF-beta-activated smad2.
PG  - 472-8
AB  - SMAD proteins are phosphorylated by transforming growth factor-beta (TGF-beta)
      receptors and translocate to the nucleus, where they control transcription. Here 
      we investigate the fate of activated Smad2. We show that receptor-mediated
      activation leads to multi-ubiquitination and subsequent degradation of Smad2 by
      the proteasome. Ubiquitination of Smad2 is a consequence of its accumulation in
      the nucleus. If degradation is averted, the phosphorylated Smad2 remains in the
      nucleus in an active state. By targeting Smad2 for destruction, TGF-beta ensures 
      the irreversible termination of its own signalling function.
FAU - Lo, R S
AU  - Lo RS
AD  - Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering
      Cancer Center, New York, New York 10021, USA.
FAU - Massague, J
AU  - Massague J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Ubiquitins)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
CIN - Nat Cell Biol. 1999 Dec;1(8):E195-7. PMID: 10587654
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/drug effects/enzymology/metabolism
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Half-Life
MH  - Humans
MH  - Models, Biological
MH  - Multienzyme Complexes/antagonists & inhibitors/metabolism
MH  - Phosphorylation/drug effects
MH  - Proteasome Endopeptidase Complex
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Signal Transduction/drug effects
MH  - Smad2 Protein
MH  - Trans-Activators/genetics/*metabolism
MH  - Transfection
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Ubiquitins/*metabolism
EDAT- 1999/12/10 09:00
MHDA- 2000/09/19 11:01
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/09/19 11:01 [medline]
PHST- 1999/12/10 09:00 [entrez]
AID - 10.1038/70258 [doi]
PST - ppublish
SO  - Nat Cell Biol. 1999 Dec;1(8):472-8. doi: 10.1038/70258.