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Titolo:
The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination
Autore:
Benvenuto, G; Li, SW; Brown, SJ; Braverman, R; Vass, WC; Cheadle, JP; Halley, DJJ; Sampson, JR; Wienecke, R; DeClue, JE;
Indirizzi:
NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales Univ Wales Coll Med Cardiff S Glam Wales CF4 4XN f CF4 4XN, S Glam, Wales Erasmus Univ, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands Erasmus Univ Rotterdam Netherlands NL-3015 GE GE Rotterdam, Netherlands Univ Munich, Dept Dermatol, Klinikum Innenstadt, D-80337 Munich, Germany Univ Munich Munich Germany D-80337 m Innenstadt, D-80337 Munich, Germany
Titolo Testata:
ONCOGENE
fascicolo: 54, volume: 19, anno: 2000,
pagine: 6306 - 6316
SICI:
0950-9232(200012)19:54<6306:TTS(GP>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
NORMAL HUMAN TISSUES; EKER RAT; NEOPLASTIC PHENOTYPE; PROTEASOME PATHWAY; RENAL-CARCINOMA; HUMAN CANCER; TARGET RAP1; IN-VIVO; PROTEIN; P53;
Keywords:
tuberous sclerosis (TSC); tumor suppressor genes; growth inhibition; ubiquitination;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: DeClue, JE NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 ar Oncol Lab, Bethesda, MD 20892 USA
Citazione:
G. Benvenuto et al., "The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination", ONCOGENE, 19(54), 2000, pp. 6306-6316

Abstract

We report here that overexpression of the tuberous sclerosis-1 (TSC1) geneproduct hamartin results in the inhibition of growth, as well as changes in cell morphology, Growth inhibition was associated with an increase in theendogenous level of the product of the tuberous sclerosis-2 (TSC2) gene, tuberin. As over-expression of tuberin inhibits cell growth, and hamartin isknown to bind tuberin, these results suggested that hamartin stabilizes tuberin and this contributes to the inhibition of cell growth. Indeed, transient transfection of TSC1 increased the endogenous level of tuberin, and transient co-transfection of TSC1 with TSC2 resulted in higher tuberin levels. The stabilization was explained by the finding that tuberin is highly ubiquitinated in cells, while the fraction of tuberin that is bound to hamartinis not ubiquitinated, Go-expression of tuberin stabilized hamartin, which is weakly ubiquitinated, in transiently transfected cells. The amino-terminal two-thirds of tuberin was responsible for its ubiquitination and for stabilization of hamartin, A mutant of tuberin from a patient missense mutation of TSC2 was also highly ubiquitinated, and was unable to stabilize hamartin, We conclude that hamartin is a growth inhibitory protein whose biological effect is likely dependent on its interaction with tuberin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 15:44:14