Open AccessNeurofibromin can inhibit Ras-dependent growth by a mechanism independent of its GTPase-accelerating function.
Author(s) -
Maureen Johnson,
Jeffrey E. DeClue,
S. Felzmann,
William C. Vass,
Guangwen Xu,
Ray White,
Douglas R. Lowy
Publication year - 1994
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.14.1.641
Subject(s) - neurofibromin 1 , biology , gtpase , gene product , microbiology and biotechnology , tumor suppressor gene , suppressor , gtpase activating protein , cell culture , cancer research , neurofibromatosis , g protein , gene , signal transduction , carcinogenesis , gene expression , genetics
The NF1 gene, which is altered in patients with type 1 neurofibromatosis, has been postulated to function as a tumor suppressor gene. The NF1 protein product neurofibromin stimulates the intrinsic GTPase activity 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, overexpression 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 neurofibromin, was inhibited in a cell line overexpressing neurofibromin, while transformation by v-raf was not altered. The results demonstrate that NF1 is a tumor suppressor gene that can inhibit Ras-dependent growth by a regulatory mechanism that is independent of neurofibromin's ability to stimulate Ras GTPase.