Abstract：
:Previously, we have shown that metastasis-associated protein 1 (MTA1) overexpression in transgenic mice was accompanied by high incidence of spontaneous B-cell lymphomas including diffuse large B-cell lymphomas (DLBCL). To understand the molecular basis of lymphoma in MTA1-transgenic (MTA1-TG) mice, we wished to identify a putative MTA1 target with a causal role in B-cell lymphogenesis. Using chromatin immunoprecipitation assays, we identified paired box gene 5 (Pax5), a molecule previously implicated in B-cell lymphogenesis, as a potential downstream effector of MTA1. Lymphomas from MTA1-TG mice also showed up-regulation of Pax5. We also found that MTA1 acetylated on Lys(626) interacted with p300 histone acetyltransferase, and that acetylated MTA1 was recruited to the Pax5 promoter to stimulate Pax5 transcription. Global gene profiling identified down-regulation of a set of genes, including those downstream of Pax5 and directly implicated in the B-cell lymphogenesis. Significance of these murine studies was established by evidence showing a widespread up-regulation of both MTA1 and Pax5 in DLBCL from humans. These observations provide in vivo genetic evidence for a role of MTA1 in lymphomagenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Balasenthil S,Gururaj AE,Talukder AH,Bagheri-Yarmand R,Arrington T,Haas BJ,Braisted JC,Kim I,Lee NH,Kumar Rdoi
10.1158/0008-5472.CAN-07-0750subject
Has Abstractpub_date
2007-08-01 00:00:00pages
7132-8issue
15eissn
0008-5472issn
1538-7445pii
67/15/7132journal_volume
67pub_type
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