PMID- 10092233
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 283
IP  - 5410
DP  - 1999 Mar 26
TI  - Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase
      2A.
PG  - 2089-91
AB  - Dysregulation of Wnt-beta-catenin signaling disrupts axis formation in vertebrate
      embryos and underlies multiple human malignancies. The adenomatous polyposis coli
      (APC) protein, axin, and glycogen synthase kinase 3beta form a Wnt-regulated
      signaling complex that mediates the phosphorylation-dependent degradation of
      beta-catenin. A protein phosphatase 2A (PP2A) regulatory subunit, B56, interacted
      with APC in the yeast two-hybrid system. Expression of B56 reduced the abundance 
      of beta-catenin and inhibited transcription of beta-catenin target genes in
      mammalian cells and Xenopus embryo explants. The B56-dependent decrease in
      beta-catenin was blocked by oncogenic mutations in beta-catenin or APC, and by
      proteasome inhibitors. B56 may direct PP2A to dephosphorylate specific components
      of the APC-dependent signaling complex and thereby inhibit Wnt signaling.
FAU - Seeling, J M
AU  - Seeling JM
AD  - Department of Oncological Sciences, Huntsman Cancer Institute, University of
      Utah, Salt Lake City, UT 84132, USA.
FAU - Miller, J R
AU  - Miller JR
FAU - Gil, R
AU  - Gil R
FAU - Moon, R T
AU  - Moon RT
FAU - White, R
AU  - White R
FAU - Virshup, D M
AU  - Virshup DM
LA  - eng
GR  - 3P30CA42014/CA/NCI NIH HHS/United States
GR  - R01 CA71074/CA/NCI NIH HHS/United States
GR  - T32CA09602/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  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (CTNNB1 protein, Xenopus)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Leupeptins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Wnt Proteins)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (beta Catenin)
RN  - 110044-82-1 (acetylleucyl-leucyl-norleucinal)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Line
MH  - Cysteine Endopeptidases/metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - Down-Regulation
MH  - Genes, Reporter
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Humans
MH  - Leupeptins/pharmacology
MH  - Multienzyme Complexes/metabolism
MH  - Mutation
MH  - Phosphoprotein Phosphatases/chemistry/genetics/*metabolism
MH  - Phosphorylation
MH  - Proteasome Endopeptidase Complex
MH  - Protein Phosphatase 2
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Signal Transduction
MH  - *Trans-Activators
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Wnt Proteins
MH  - Xenopus
MH  - Xenopus Proteins
MH  - *Zebrafish Proteins
MH  - beta Catenin
EDAT- 1999/03/26 00:00
MHDA- 1999/03/26 00:01
CRDT- 1999/03/26 00:00
PHST- 1999/03/26 00:00 [pubmed]
PHST- 1999/03/26 00:01 [medline]
PHST- 1999/03/26 00:00 [entrez]
AID - 10.1126/science.283.5410.2089 [doi]
PST - ppublish
SO  - Science. 1999 Mar 26;283(5410):2089-91. doi: 10.1126/science.283.5410.2089.