Cure of human immunodeficiency virus/acquired immune deficiency syndrome: promising future prospects at horizon

Acquired immune deficiency syndrome (AIDS) is a disease caused by humanimmunodeficiency virus and characterized by profound immunosuppression thatleads to opportunistic infections, secondary neoplasms, and neurologic complications.AIDS is among the leading causes of death worldwide. Current therapeutic optionsare directed only toward management of AIDS, but not toward its prevention or cure.In addition, it also possesses numerous problems like drug resistance, drug toxicity,drug interactions, non-adherence to therapy, life-long and expensive treatment, etc.Recent years in drug development have shown promising prospects for prevention/treatment/cure of AIDS like histone deacetylase inhibitors, Vpu ion channel inhibitors,viral decay acceleration, maturation inhibitors, tat antagonists, gene/stem cell therapy,and antiretroviral vaccines

Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis

The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis