PMID- 10023660
OWN - NLM
STAT- MEDLINE
DCOM- 19990223
LR  - 20171116
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Jan 28
TI  - The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and
      regulates the stability of beta-catenin.
PG  - 849-54
AB  - Ubiquitin-conjugation targets numerous cellular regulators for
      proteasome-mediated degradation. Thus, the identification of ubiquitin ligases
      and their physiological substrates is crucially important, especially for those
      cases in which aberrant levels of regulatory proteins (e.g., beta-catenin, p27)
      result from a deregulated ubiquitination pathway. In yeast, the proteolysis of
      several G1 regulators is controlled by ubiquitin ligases (or SCFs) formed by
      three subunits: Skp1, Cul A (Cdc53), and one of many F-box proteins. Specific
      F-box proteins (Fbps) recruit different substrates to the SCF. Although many Fbps
      have been identified in mammals, their specific substrates and the existence of
      multiple SCFs have not yet been reported. We have found that one human Fbp,
      beta-Trcp (beta-Transducin repeat containing protein), does indeed form a novel
      SCF with human Skp1 and Cul1. Consistent with recent reports indicating that
      Xenopus and Drosophila beta-Trcp homologs act as negative regulators of the
      Wnt/beta-catenin signaling pathway, we report here that human beta-Trcp interacts
      with beta-catenin in vivo. Furthermore, beta-catenin is specifically stabilized
      in vivo by the expression of a dominant negative beta-Trcp. These results
      indicate that the Cul1/Skp1/beta-Trcp complex forms a ubiquitin ligase that
      mediates the degradation of beta-catenin.
FAU - Latres, E
AU  - Latres E
AD  - Department of Pathology and Kaplan Comprehensive Cancer Center, New York
      University Medical Center, NY 10016, USA.
FAU - Chiaur, D S
AU  - Chiaur DS
FAU - Pagano, M
AU  - Pagano M
LA  - eng
GR  - 5T32-CA09161/CA/NCI NIH HHS/United States
GR  - R01-CA76584/CA/NCI NIH HHS/United States
GR  - R01-GM57587/GM/NIGMS 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  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (BTRC protein, human)
RN  - 0 (CD4 Antigens)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Ubiquitins)
RN  - 0 (beta Catenin)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - CD4 Antigens/metabolism
MH  - Cell Cycle Proteins/*metabolism
MH  - Cells, Cultured
MH  - Cytoskeletal Proteins/*metabolism
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - Ligases/*metabolism
MH  - S-Phase Kinase-Associated Proteins
MH  - Substrate Specificity
MH  - *Trans-Activators
MH  - Ubiquitins/metabolism
MH  - beta Catenin
MH  - beta-Transducin Repeat-Containing Proteins
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
AID - 10.1038/sj.onc.1202653 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jan 28;18(4):849-54. doi: 10.1038/sj.onc.1202653.