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p73, the first p53 gene homologue, encodes an array of p73 proteins including p73α full-length (TAp73α) and amino-truncated isoforms (ΔNp73α), two proteins with opposite biological functions. TAp73α can induce tumor suppressive properties, while ΔNp73α antagonizes p53 as well as TAp73 in a dominant-negative manner. In human malignant neuroblasts, p53 protein is wild-type but known to be excluded from the nucleus, therefore disabling its function as a tumor suppressor. The present study investigates whether there is a functional link between p73 isoforms and p53 in neuroblastoma. Experiments were performed on two neuroblastoma cell lines differing in their p53 status, e.g. wild-type p53 SH-5Y5Y cells and mutated p53 IGR-N-91 cells. Data indicate that (i) both TA- and ΔN-p73α enhance p53 protein level in SH-SY5Y cells, whereas level remains unchanged in IGR-N-91 cells; (ii) only in SH-SY5Y cells does forced TAp73α overexpression markedly induce nuclear accumulation of p53 protein; (iii) p21 protein expression is increased in both cell lines infected with TAp73, suggesting that, in IGR-N-91 cells, p21 is induced by p73 through a p53-independent pathway; (iv) in the SHSY5Y cell line, Btg2 expression is strongly enhanced in cells overexpressing TA, and to a lesser extent in cells overexpressing ΔN. Taken together our results suggest that TAp73 may restore p53 function in NB with wild-type nonfunctional p53, but not in NB with mutated p53.

Partial Beclin 1 silencing aggravates mitochondrial permeabilization and apoptosis in HepG2 cells treated with an anti-Fas antibody or with doxorubicin.

Understanding the distribution, function, and lineage relationship of CD8 ؉ T-cell subpopulations is of fundamental value for the monitoring of the immune system in several experimental and clinical situations. However, the available data concerning the description of effector and memory CD8 ؉ subsets in humans remain rather fragmentary because different studies favored the usage of distinct and restricted sets of cell surface markers and functional parameters. We associated multiple markers to subdivide CD8 ؉ T cells into 14 different cell types, several of which were not described previously, and evaluated the coexpression of 18 genes simultaneously in individual cells from each subset. Our results show that each subset has a defined pattern of gene expression. Moreover, effector gene expression of CCR7 ؊ cells correlated only with CD27 expression levels and CD27/ CD28 coexpression but not with CD45RA/R0 phenotypes. Our findings thus describe new CD8 ؉ cell subsets, allow the identification of relatively homogeneous CD8 ؉ subpopulations, provide a predictable and precise correlation between particular cell surface markers and CD8 ؉ T-cell functional properties, and identify effector cells present in both CCR7 ؊ CD45RA ؉ and CCR7 ؊ CD45R0 ؉ compartments. The results also indicate that activated cells might modulate the expression of CD45RA/R0 asynchronously rather than CCR7 ؊ CD45RA ؉ cells always issuing from CD45RA ؊ precur-