Journal article
The 48-kDa Alternative Translation Isoform of PP2A:B56ε Is Required for Wnt Signaling during Midbrain-Hindbrain Boundary Formation
The Journal of biological chemistry, Vol.284(11), pp.7190-7200
03/13/2009
DOI: 10.1074/jbc.M807907200
PMCID: PMC2652268
PMID: 19129191
Abstract
Alternative translation is an underappreciated post-transcriptional
regulation mechanism. Although only a small number of genes are found to be
alternatively translated, most genes undergoing alternative translation play
important roles in tumorigenesis and development. Protein phosphatase 2A
(PP2A) is involved in many cellular events during tumorigenesis and
development. The specificity, localization, and activity of PP2A are regulated
by B regulatory subunits. B56ε, a member of the B56 regulatory subunit
family, is involved in multiple signaling pathways and regulates a number of
developmental processes. Here we report that B56ε is alternatively
translated, leading to the production of a full-length form and a shorter
isoform that lacks the N-terminal 76 amino acid residues of the full-length
form. Alternative translation of B56ε occurs through a cap-dependent
mechanism. We provide evidence that the shorter isoform is required for Wnt
signaling and regulates the midbrain/hindbrain boundary formation during
Xenopus
embryonic development. This demonstrates that the shorter
isoform of B56ε has important biological functions. Furthermore, we show
that the N-terminal sequence of B56ε, which is not present in the shorter
isoform, contains a nuclear localization signal, whereas the C terminus of
B56ε contains a nuclear export signal. The shorter isoform, which lacks
the N-terminal nuclear localization signal, is restricted to the cytoplasm. In
contrast, the full-length form can be localized to the nucleus in a cell
type-specific manner. The finding that B56ε is alternatively translated
adds a new level of regulation to PP2A holoenzymes.
Details
- Title: Subtitle
- The 48-kDa Alternative Translation Isoform of PP2A:B56ε Is Required for Wnt Signaling during Midbrain-Hindbrain Boundary Formation
- Creators
- Zhigang Jin - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theJianli Shi - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theAmit Saraf - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theWenyan Mei - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theGuo-Zhang Zhu - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theStefan Strack - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, theJing Yang - Center for Cell and Development Biology, the Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.284(11), pp.7190-7200
- DOI
- 10.1074/jbc.M807907200
- PMID
- 19129191
- PMCID
- PMC2652268
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 03/13/2009
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040252302771
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