Abstract:
:A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity is relevant for tumor growth. Here we report that MALT1 is constitutively active in DLBCL lines of the ABC but not the GCB subtype. Inhibition of the MALT1 proteolytic activity led to reduced expression of growth factors and apoptosis inhibitors, and specifically affected the growth and survival of ABC DLBCL lines. These results demonstrate a key role for the proteolytic activity of MALT1 in DLBCL of the ABC subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Hailfinger S,Lenz G,Ngo V,Posvitz-Fejfar A,Rebeaud F,Guzzardi M,Penas EM,Dierlamm J,Chan WC,Staudt LM,Thome Mdoi
10.1073/pnas.0907511106subject
Has Abstractpub_date
2009-11-24 00:00:00pages
19946-51issue
47eissn
0027-8424issn
1091-6490pii
0907511106journal_volume
106pub_type
杂志文章abstract::Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygda...
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