N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo

作者：Momose Shuji; Kobayashi Toshiyuki; Tada Norihiro; Itoyama Shinji; Hino Okio^*

来源：Biochemical and Biophysical Research Communications, 2007, 356(3): 693-698.

DOI：10.1016/j.bbrc.2007.03.036

• Tsc2
• tuberin
• Eker rat
• transgenic rat

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 carboxyterminal 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.

• 出版日期2007-5-11