Ricerc@Sapienza

Unfolded protein response (UPR) is a conserved adaptive response that tries to restore protein homeostasis after endoplasmic reticulum (ER) stress. Recent studies highlighted the role of UPR in acute leukemias and UPR targeting has been suggested as a therapeutic approach. Aberrant Notch signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), as downregulation of Notch activity negatively affects T-ALL cell survival, leading to the employment of Notch inhibitors in T-ALL therapy.

Aberrant Notch signaling is involved in the development of several diseases, including T-cell acute lymphoblastic leukemia (T-ALL). A better knowledge of T-ALL biology has opened opportunities for the development of targeted therapies for the treatment of this disease. Recently, several studies suggest the role of the unfolded protein response (UPR) in acute leukemias. Juglone, a naturally-occurring naphtoquinone, is considered a promising anticancer agent for its strong activity against cancer cells in in vitro and in vivo models, including leukemia.

Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated
the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end,
we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient
cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of

Herpesviruses are known to manipulate autophagy to optimize their replication, counteract immune response and probably to promote tumourigenesis. This study explored, for the first time, the impact of human herpesvirus (HHV)-6 lytic infection on autophagy and demonstrated that HHV-6A and B (viruses sharing more than 80 % homology) differently affected this cellular process. Indeed, while HHV-6A (GS) infection of HSB2 cells promoted autophagy, HHV-6B (Z29) or the virus isolated from the serum of roseola infantum-affected patient-inhibited autophagy in Molt-3 cells or in PBMCs, respectively.

A plethora of studies has indicated that ageing is characterized by an altered proteostasis, ROS accumulation and a status of mild/chronic inflammation, in which macroautophagy reduction and abnormal UPR activation play a pivotal role. The dysregulation of these inter-connected processes favors immune dysfunction and predisposes to a variety of several apparently unrelated pathological conditions including cancer and neurodegeneration.