Molecular and Cellular Biology ( MCB ) is devoted to the advancement and dissemination of fundamental knowledge concerning the molecular biology of all eukaryotic cells. MCB seeks technically rigorous, mechanistic studies that provide significant advances in the areas of gene expression and genome organization, cellular morphology and function, molecular metabolism, cellular trafficking, and signal transduction. The journal is also interested in studies that investigate molecular, cellular, and systemic host responses to pathogenic agents in chronic diseases and conditions. MCB is edited by leading investigators in the field of molecular biology, and decisions are based solely on scientific merit. MCB recognizes that rigorous, in-depth extensions of prior observations contribute in an important way to the advancement of scientific knowledge. We welcome studies that build upon, clarify, or question previous work and thereby move the field forward.
Maureen Johnson, Jeffrey E. DeClue, Sylvia Felzmann, William C. Vass, Gangfeng Xu, R. White, Douglas R. Lowy
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.
Saccharomyces cerevisiae contains two genes which encode cyclic AMP (cAMP) phosphodiesterase. We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S. cerevisiae, which encodes a low-affinity cAMP phosphodiesterase. These two genes represent highly divergent branches in the evolution of phosphodiesterases. High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation. PDE1 and PDE2 appear to account for the aggregate cAMP phosphodiesterase activity of S. cerevisiae. Disruption of both PDE genes results in a phenotype which resembles that induced by the RAS2(Val-19) mutation. pde1- pde2- ras1- ras2- cells are viable.