The paracaspase MALT1 controls caspase-8 activation during lymphocyte proliferation.

Caspase-8, an initiator caspase involved in lymphocyte apoptosis, is paradoxically required for lymphocyte proliferation. It is not understood how caspase-8 is controlled during antigenic signaling to allow for activation while averting the triggering of apoptosis. Here, we show that caspase-8 undergoes limited activation upon antigenic stimulation, and this activation is dependent on the paracaspase MALT1.

Lys63-linked polyubiquitin chains: linking more than just ubiquitin.

Polyubiquitin chains linked through the Lys48 residue of ubiquitin are most commonly associated with targeting proteins for proteosomal degradation. In contrast, polyubiquitin chains linked through the Lys63 residue of ubiquitin are associated with nonproteolytic functions such as signal transduction. The mechanism by which Lys63-linked polyubiquitin chains participate in signaling cascades has yet to be determined, but two recent publications (Wu et al.

A novel fusion of the MALT1 gene and the microtubule-associated protein 4 (MAP4) gene occurs in diffuse large B-cell lymphoma.

Rearrangements of the MALT1 gene by the t(11;18)(q21;q21) and t(14;18)(q32;q21) are the most frequent structural chromosomal abnormalities in MALT lymphomas. These translocations lead to fusions of BIRC3-MALT1 and IGH-MALT1 respectively, and activate the NF-kappaB pathway. Among 122 diffuse large B-cell lymphomas and 28 Burkitt's lymphomas screened by interphase FISH, we found two cases with a break within MALT1, but without a t(11;18) or a t(14;18).

Lymphocyte life and death: the caspase-8 connection.

Caspase-8 plays an important role in death receptor-mediated apoptosis. In contrast to its apoptotic function, recent studies have suggested caspase-8 also plays a role in the immune response, as caspase-8 is essential for lymphocyte proliferation in response to antigen stimulation. In the March 2005 issue of Science (2005; 307:1465-8), Su et al.