N-terminal Hamartin-binding and C-terminal Gap Domain of Tuberin Can Separate in Vivo.
From: Department of Pathology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda-tsujimichi, Kawagoe, Saitama 350-8550, Japan.
Biochemical and biophysical research communications
- Publish Date: May 2007
- ISSN: 0006-291X
- Volume: 356
- Issue: 3
- Pages: 693-8
- Medium: Print
- Language: English
- Citation (JAMA): Momose Shuji, Kobayashi Toshiyuki, Tada Norihiro, et al. N-terminal Hamartin-binding and C-terminal Gap Domain of Tuberin Can Separate in Vivo.. Biochem. Biophys. Res. Commun. May 2007;356:693-8
Abstract
The Eker rat is an animal model of renal carcinogenesis and carries a transposon insertion in the Tsc2 (tuberous sclerosis-2) gene. We previously generated transgenic Eker rats and identified coding sequences in the Tsc2 gene that are responsible for suppression of renal carcinogenesis in Eker rats. Tsc2-RGH, a transgene that expresses the carboxy terminal region (amino acids 1425-1755) of the Tsc2 product (tuberin), partially suppressed renal carcinogenesis. However, Tsc2-DRG, which expresses a mutant tuberin lacking the carboxy-terminal region (Delta aa 1425-1755), did not suppress renal carcinogenesis. Here, we found that introduction of both Tsc2-RGH and Tsc2-DRG in Eker rats completely suppressed renal carcinogenesis and rescued homozygous (Tsc2(Ek/Ek)) mutants from embryonic lethality in a complementary manner. Co-introduction of Tsc2-RGH and Tsc2-DRG, but not introduction of either alone, efficiently suppressed phosphorylation of p70 S6K. Thus, the functional domains of N-terminal hamartin binding and C-terminal tumor suppression in tuberin can separate in vivo.
Mesh Headings (Keywords): Animals, Animals, Genetically Modified, Ethylnitrosourea, Extracellular Signal-Regulated MAP Kinases, GTPase-Activating Proteins, Kidney, Kidney Neoplasms, Protein Structure, Tertiary, Rats, Signal Transduction, Tumor Suppressor Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17379185
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