Here we identified cellular apoptosis susceptibility (CAS, exportin-2) and its transport substrate importin-alpha 1 (imp-alpha 1) among significantly up-regulated transport factor genes in HCC. Disruption of the CAS/imp-alpha 1 transport cycle by RNAi in HCC cell lines resulted in decreased tumor cell growth and increased apoptosis. The apoptotic phenotype upon CAS depletion could be recapitulated
by direct knockdown of the X-linked inhibitor of apoptosis (XIAP) and partially reverted by XIAP overexpression. In addition, XIAP and CAS mRNA expression levels were correlated in HCC patient samples (r = 0.463; P smaller than 0.01), supporting the in vivo relevance of our findings. Furthermore, quantitative mass spectrometry analyses of murine HCC samples (p53-/- versus p53+/+) indicated higher protein expression of CAS and check details imp-alpha 1 in p53-/- tumors. Consistent with a role
of p53 in regulating the CAS/imp-alpha 1 transport cycle, we observed that both transport factors were repressed upon p53 induction in a p21-dependent manner. Conclusion: The CAS/imp-alpha 1 transport cycle is linked to XIAP and is required to maintain tumor cell survival in HCC. Moreover, CAS and imp-alpha 1 are selleck chemicals targets of p53-mediated repression, which represents a novel aspect of p53′s ability to control tumor cell growth in hepatocarcinogenesis.”
“Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified pUL135 BEZ235 manufacturer as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation.
An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix.”
“The authors present the cases of 3 patients with ruptured perforator aneurysms of the posterior circulation. Patients were 39,55, and 59 years old. None of the patients had relevant past medical or family history. All presented with World Federation of Neurosurgical Societies Grade I and Fisher Grade 2 or 3 subarachnoid hemorrhage. Initial angiography results were normal.