A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

A Novel Myc Target Gene, mina53, That Is Involved in Cell Proliferation

“…But the transactivation of these genes by c-Myc is generally weak, between two to severalfold. Attempts to identify genes capable of re-establishing normal proliferative rates in c-mycϪ/Ϫ cells have resulted in the repeated identification of c-myc and N-myc (16,17). These results suggest that myc controls not a gene but genes to regulate cell proliferation.…”

Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts

“…However, this effect could be derivative of a benefit to c-Myc-mediated proliferation, because T antigen requires c-myc activity to drive cell proliferation. 42 The growth inhibitory effects of Bin1 could not be mediated by the p53 or Rb pathways, because p53 was inactivated by targeted gene deletion or T antigen binding in the MR and TR cells, respectively, and because Rb was suppressed by Myc activity or T antigen binding in the MR and TR MEFs, respectively. 43,44 We conclude that Bin1 restrains anchorage-independent cell proliferation through a p53/Rb-independent mechanism.…”

“…Therefore, to examine this question we used MEFs transformed by the adenovirus E1A early region plus activated H-ras (termed ER MEFs or ER cells) that had been generated for another study. 15 The relevance of this system is justified by functional similarity between c-myc and E1A in murine cell transformation, 48 the requirement of c-myc for E1A to drive cell proliferation, 42 and the well-documented ability of the E1A early region to sensitize murine fibroblasts to TNF-induced apoptosis (e.g., ref. 49).…”

Disentangling the MYC web

“…MYC overexpression, misexpression, and deregulation generally increase rates of cellular proliferation and growth, with accompanying inhibition of differentiation, but in some circumstances, elevated MYC provokes apoptosis (4,5). No single MYC target, validated or proposed, seems to account fully for the biological effects of MYC; none could be related to MYC in a single linear effector pathway or by epistasis (19). A deficiency of Myc can be rescued only by MYC itself or the highly related N-myc oncogene or MYC itself.…”