Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2013 May 3;288(18):12766-76. doi: 10.1074/jbc.M112.429696. Epub 2013 Mar 21.

Fas-associated phosphatase 1 (Fap1) influences βcatenin activity in myeloid progenitor cells expressing the Bcr-abl oncogene.

Author information

1
Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA.

Abstract

Increased βcatenin activity correlates with leukemia stem cell expansion and disease progression in chronic myeloid leukemia (CML). We found previously that expression of the CML-related Bcr-abl oncoprotein in myeloid progenitor cells increases expression of Fas-associated phosphatase 1 (Fap1). This resulted in Fap1-dependent resistance to Fas-induced apoptosis in these cells. Fap1 also interacts with the adenomatous polyposis coli (Apc) protein, but the functional significance of this interaction is unknown. Apc participates in a complex that includes glycogen synthase kinase β (Gsk3β) and βcatenin. Assembly of this complex results in phosphorylation of βcatenin by Gsk3β, which facilitates βcatenin ubiquitination and degradation by the proteasome. In this study, we found increased association of Fap1 with the Apc complex in Bcr-abl(+) myeloid progenitor cells. We also found Fap1-dependent inactivation of Gsk3β and consequent stabilization of βcatenin in these cells. Consistent with this, Bcr-abl(+) cells exhibited a Fap1-dependent increase in βcatenin activity. Our studies identified Fap1-dependent Gsk3β inactivation as a molecular mechanism for increased βcatenin activity in CML.

KEYWORDS:

Fas; Gene Regulation; Glycogen Synthase Kinase 3; Leukemia; βcatenin

PMID:
23519466
PMCID:
PMC3642322
DOI:
10.1074/jbc.M112.429696
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center