PMID- 10458166
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20161124
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6745
DP  - 1999 Aug 12
TI  - A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern
      formation.
PG  - 687-93
AB  - The TGF-beta superfamily of proteins regulates many different biological
      processes, including cell growth, differentiation and embryonic pattern
      formation. TGF-beta-like factors signal across cell membranes through complexes
      of transmembrane receptors known as type I and type II serine/threonine-kinase
      receptors, which in turn activate the SMAD signalling pathway. On the inside of
      the cell membrane, a receptor-regulated class of SMADs are phosphorylated by the 
      type-I-receptor kinase. In this way, receptors for different factors are able to 
      pass on specific signals along the pathway: for example, receptors for bone
      morphogenetic protein (BMP) target SMADs 1, 5 and 8, whereas receptors for
      activin and TGF-beta target SMADs 2 and 3. Phosphorylation of receptor-regulated 
      SMADs induces their association with Smad4, the 'common-partner' SMAD, and
      stimulates accumulation of this complex in the nucleus, where it regulates
      transcriptional responses. Here we describe Smurf1, a new member of the Hect
      family of E3 ubiquitin ligases. Smurf1 selectively interacts with
      receptor-regulated SMADs specific for the BMP pathway in order to trigger their
      ubiquitination and degradation, and hence their inactivation. In the amphibian
      Xenopus laevis, Smurf1 messenger RNA is localized to the animal pole of the egg; 
      in Xenopus embryos, ectopic Smurf1 inhibits the transmission of BMP signals and
      thereby affects pattern formation. Smurf1 also enhances cellular responsiveness
      to the Smad2 (activin/TGF-beta) pathway. Thus, targeted ubiquitination of SMADs
      may serve to control both embryonic development and a wide variety of cellular
      responses to TGF-beta signals.
FAU - Zhu, H
AU  - Zhu H
AD  - Department of Biochemistry and Cell Biology and Institute for Cell and
      Developmental Biology, State University of New York, Stony Brook 11794-5215, USA.
FAU - Kavsak, P
AU  - Kavsak P
FAU - Abdollah, S
AU  - Abdollah S
FAU - Wrana, J L
AU  - Wrana JL
FAU - Thomsen, G H
AU  - Thomsen GH
LA  - eng
SI  - GENBANK/AF169310
SI  - GENBANK/AF199364
GR  - R01 HD032429/HD/NICHD NIH HHS/United States
GR  - R01 HD032429-04/HD/NICHD NIH HHS/United States
GR  - R01 HD032429-05/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD5 protein, human)
RN  - 0 (Smad Proteins)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, Xenopus)
RN  - 0 (Smad5 Protein)
RN  - 0 (Smad5 protein, Xenopus)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Ubiquitins)
RN  - 0 (Xenopus Proteins)
RN  - EC 2.3.2.26 (SMURF1 protein, Xenopus)
RN  - EC 2.3.2.26 (SMURF2 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Animals
MH  - Body Patterning/*physiology
MH  - Bone Morphogenetic Proteins/*metabolism
MH  - COS Cells
MH  - Cell Line
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/*metabolism
MH  - Ectoderm/metabolism
MH  - Embryo, Nonmammalian/metabolism
MH  - Humans
MH  - Ligases/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Phosphoproteins/metabolism
MH  - *Signal Transduction
MH  - Smad Proteins
MH  - Smad2 Protein
MH  - Smad5 Protein
MH  - Trans-Activators/*metabolism
MH  - Transforming Growth Factor beta/metabolism
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/metabolism
MH  - Xenopus
MH  - Xenopus Proteins
EDAT- 1999/08/24 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/08/24 10:00
PHST- 1999/08/24 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/08/24 10:00 [entrez]
AID - 10.1038/23293 [doi]
PST - ppublish
SO  - Nature. 1999 Aug 12;400(6745):687-93. doi: 10.1038/23293.