Search

The Ink4a/Arf locus encodes [p16.sup.Ink4a] and [p19.sup.Arf] and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between [p19.sup.Arf] and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both [p16.sup.Ink4a] and [p19.sup.Arf] are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis. Because expression of [p19.sup.Arf] but not [p16.sup.Ink4a] induced apoptosis in Ab-MLV-transformed pre-B cells, [p19.sup.Arf] appears to be responsible for these events. Consistent with the link between [p19.sup.Arf] and p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that [p19.sup.Arf] is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the [p19.sup.Arf] - p53 regulatory loop plays an important role in lymphoma induction.

Abstract Mycophenolate mofetil is commonly used as a steroid-sparing agent effective in the management of erythema nodosum, idiopathic nodular panniculitis (Pfiefer-Weber-Christian disease), bullous pemphigoid, pemphigus vulgaris, and psoriasis. We report [...]