The ubiquitin C-terminal hydrolase UCH-L1 regulates B-cell proliferation and integrin activation.

The ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a deubiquitinating enzyme that catalyses the hydrolysis of polyubiquitin precursors and small ubiquitin adducts. UCH-L1 has been detected in a variety of malignant and metastatic tumours but its biological function in these cells is unknown. We have previously shown that UCH-L1 is highly expressed in Burkitt's lymphoma (BL) and is up-regulated upon infection of B lymphocytes with Epstein-Barr virus (EBV).

Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children.

HIV-1 infection induces a progressive disruption of the B cell compartment impairing long-term immune responses to routine immunizations. Depletion of specific memory B cell pools occurs during the 1st stages of the infection and cannot be reestablished by antiretroviral treatment. We reasoned that an early control of viral replication through treatment could preserve the normal development of the memory B cell compartment and responses to routine childhood vaccines.

Switching from protease inhibitor-based-HAART to a protease inhibitor-sparing regimen is associated with improved specific HIV-immune responses in HIV-infected children.

To evaluate the effects of switching from successful long-term protease inhibitor (PI)-based HAART to a three nucleoside reverse transcriptase inhibitor PI-sparing regimen, viral load quantification, HIV-specific lymphoproliferative assay and T-cell receptor (TCR) spectratyping were performed during 96 weeks of simplification follow-up in 19 HIV-infected children. Our data showed that simplification of therapeutic strategies acts positively on immune competence in HIV paediatric patients. Our children maintained viral suppression, increased lymphoproliferative responses and normalized TCRBV repertoire on the CD8 subset.

TPPII promotes genetic instability by allowing the escape from apoptosis of cells with activated mitotic checkpoints.

Overexpression of TPPII correlates with accelerated growth and the appearance of centrosome and chromosome aberrations, suggesting that the activity of this enzyme may be critical for the induction and/or maintenance of genetic instability in malignant cells. We now find that the length of mitosis and of the entire cell cycle is significantly reduced in TPPII overexpressing HEK293 cells compared to untransfected and control transfected cells. Functional TPPII knockdown by shRNA interference caused a significant slowdown in cell growth and the accumulation of cells that delayed or failed to complete mitosis.