| First Author | Hailfinger S | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 35 | Pages | 14596-601 |
| PubMed ID | 21873235 | Mgi Jnum | J:175215 |
| Mgi Id | MGI:5284995 | Doi | 10.1073/pnas.1105020108 |
| Citation | Hailfinger S, et al. (2011) Malt1-dependent RelB cleavage promotes canonical NF-{kappa}B activation in lymphocytes and lymphoma cell lines. Proc Natl Acad Sci U S A 108(35):14596-601 |
| abstractText | The protease activity of the paracaspase Malt1 contributes to antigen receptor-mediated lymphocyte activation and lymphomagenesis. Malt1 activity is required for optimal NF-kappaB activation, but little is known about the responsible substrate(s). Here we report that Malt1 cleaved the NF-kappaB family member RelB after Arg-85. RelB cleavage induced its proteasomal degradation and specifically controlled DNA binding of RelA- or c-Rel-containing NF-kappaB complexes. Overexpression of RelB inhibited expression of canonical NF-kappaB target genes and led to impaired survival of diffuse large B-cell lymphoma cell lines characterized by constitutive Malt1 activity. These findings identify a central role for Malt1-dependent RelB cleavage in canonical NF-kappaB activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment. |
