Immunoprecipitation experiments revealed that the Ii chain can interact with Nef in a dileucine-dependent manner. Importantly, we have shown that Nef-induced CD4 downregulation and Ii chain upregulation are genetically selleck distinguishable. We have identified natural nef alleles that have lost one of the two functions but not the other one. Moreover, we have characterized Nef mutant forms possessing

a similar phenotype in the context of HIV-1 infection. Therefore, the Nef-induced accumulation of Ii chain complexes at the cell surface probably results from a complex mechanism leading to the impairment of AP-2-mediated endocytosis rather than from direct competition between Nef and the Ii chain for binding AP-2.”
“Transformation by Abelson

murine leukemia virus (Ab-MLV) is a multistep process in which growth-stimulatory signals from the v-Abl oncoprotein and growth-suppressive signals from the p19(Arf)-p53 tumor suppressor pathway oppose each other and influence the outcome of infection. The process involves a proliferative phase during which highly viable primary transformants expand, followed by a period of marked apoptosis (called “”crisis”") Defactinib that is dependent on the presence of P19(Arf) and p53; rare cells that survive this phase emerge as fully transformed and malignant. To understand the way in which v-Abl expression affects P19(Arf) expression, we examined changes in expression of Arf during all stages of Ab-MLV transformation process. As is consistent with the ability of v-Abl to stimulate Myc, a transcription factor known to induce p19(Arf), Myc and Arf are induced soon after infection and p19(Arf) is expressed. At these early time points, the infected cells remain highly viable. The onset of crisis is marked by an increase in P19(Arf) expression and a change in localization of the protein from the nucleoplasm to the nucleolus. These

data together suggest that the localization and expression levels of p19(Arf) modulate the effects of the protein during oncogenesis and reveal that the p19(Arf)-mediated response is subject to multiple layers of regulation that influence its function during Ab-MLV-mediated transformation.”
“The mechanism by which herpes simplex selleck compound virus (HSV) exits the nucleus remains a matter of controversy. The generally accepted route proposes that capsids exit via primary envelopment at the inner nuclear membrane and subsequent fusion of this primary particle with the outer nuclear membrane to gain capsid entry to the cytoplasm. However, recent observations indicate that HSV may induce gross morphological alterations of nuclear pores, resulting in the loss of normal pores and the appearance of dilated gaps in the nuclear membrane of up to several 100 nm.