Tuberin negatively affects BCL-2's cell survival function.
Uncontrolled cell cycle progression and cell growth are key properties of tumor cells. The tumor suppressor genes responsible for the autosomal dominantly inherited disease tuberous sclerosis (TSC) have been demonstrated to control both, cell cycle and cell size regulation. Hamartin, encoded by TSC1, and tuberin, encoded by TSC2, form a complex, of which tuberin is assumed to be the functional component. Loss of TSC genes function triggers hamartoma development in TSC patients. However, in vivo mostly tumor cell development is rapidly terminated via apoptosis. BCL-2, the founding member of the BCL-2 family of proteins, is well known for its anti-apoptotic properties. Here we show that pro-apoptotic actinomycin D cannot interfere with BCL-2's cell survival functions. However, we found tuberin to negatively regulate BCL-2's anti-apoptotic effects on low serum-induced apoptosis. These findings warrant further investigations to elucidate the molecular mechanism underlying tuberin's negative effects on cell survival.
Freilinger
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A
Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
Rosner
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M
Hengstschläger
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M
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D003609:Dactinomycin