NEUROFIBROMIN CAN INHIBIT RAS-DEPENDENT GROWTH BY A MECHANISM INDEPENDENT OF ITS GTPASE-ACCELERATING FUNCTION

Citation
Mr. Johnson et al., NEUROFIBROMIN CAN INHIBIT RAS-DEPENDENT GROWTH BY A MECHANISM INDEPENDENT OF ITS GTPASE-ACCELERATING FUNCTION, Molecular and cellular biology, 14(1), 1994, pp. 641-645
Citations number
35
Categorie Soggetti
Biology
ISSN journal
02707306
Volume
14
Issue
1
Year of publication
1994
Pages
641 - 645
Database
ISI
SICI code
0270-7306(1994)14:1<641:NCIRGB>2.0.ZU;2-Z
Abstract
The NF1 gene, which is altered in patients with type 1 neurofibromatos is, has been postulated to function as a tumor suppressor gene. The NF 1 protein product neurofibromin stimulates the intrinsic GTPase activi ty of active GTP-bound Ras, thereby inactivating it. Consistent with a tumor suppressor function, we have found that the introduction of NF1 in melanoma cell lines that are deficient in neurofibromin inhibited their growth and induced their differentiation. In addition, overexpre ssion of neurofibromin in NIH 3T3 cells was growth inhibitory but did not alter the level of GTP . Ras in the cells. Transformation by v-ras , whose protein product is resistant to GTPase stimulation by neurofib romin, was inhibited in a cell line overexpressing neurofibromin, whil e transformation by v-raf was not altered. The results demonstrate tha t NF1 is a tumor suppressor gene that can inhibit Ras-dependent growth by a regulatory mechanism that is independent of neurofibromin's abil ity to stimulate Ras GTPase.