NDLI: Internal Translation Initiation Generates Novel WT1 Protein Isoforms with Distinct Biological Properties

Content Provider	Journal of Biological Chemistry (JBC)
Author	Scharnhorst, Volkher Dekker, Patrick Eb, Alex J. Van Der Jochemsen, Aart G.
Abstract	The Wilms’ tumor 1 gene, WT1, is homozygously mutated in a subset of Wilms’ tumors. Heterozygous mutations in WT1 give rise to congenital anomalies. During embryogenesis, WT1 is expressed mainly in the kidneys, uterus, and testes.Alternative splicing of the WT1 mRNA results in synthesis of four main WT1 protein isoforms with molecular masses of 52–54 kDa. In addition, translation initiation at a CUG upstream of the initiator AUG generates four larger WT1 proteins of 60–62 kDa.We describe here the existence of novel WT1 isoforms and demonstrate that they are derived from translation initiation at the second in-frame AUG of the WT1 mRNA. These N-terminally truncated WT1 proteins of 36–38 kDa can be detected in several cell lines, mouse testes, and Wilms’ tumor specimens. They can bind to DNA and direct transcription from reporter constructs. The shorter WT1 protein lacking the two splice inserts has a greater transcription activation potential than the corresponding main WT1 protein isoform but shows no transcription repression potential. Overexpression of full-length or N-terminally truncated WT1 efficiently induces apoptosis. These data show that additional WT1 isoforms with distinct transcription-regulatory properties exist, which further increases the complexity of WT1 expression and activity.
Related Links	http://www.jbc.org/content/274/33/23456.abstract
Ending Page	23462
Starting Page	23456
Page Count	7
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	33
Volume Number	274
DOI	10.1074/jbc.274.33.23456
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1999-08-13
Access Restriction	Open
Subject Keyword	Wilms’ tumor (WT) Insulin-like growth factor II (IGFII) Adenovirus-transformed baby-rat kidney (AdBRK) 4,6-diamidino-2-phenylindole (DAPI) Β-galactosidase (LacZ) Cytomegalovirus immediate early (CMV) NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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