Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Molecular and Cellular Biology
Year: 2008  |  Volume: 28  |  Issue: 17  |  Page No.: 5391 - 5402

Selection against PUMA Gene Expression in Myc-Driven B-Cell Lymphomagenesis

Sean P. Garrison, John R. Jeffers, Chunying Yang, Jonas A. Nilsson, Mark A. Hall, Jerold E. Rehg, Wen Yue, Jian Yu, Lin Zhang, Mihaela Onciu, Jeffery T. Sample, John L. Cleveland and Gerard P. Zambetti    

Abstract: The p53 tumor suppressor pathway limits oncogenesis by inducing cell cycle arrest or apoptosis. A key p53 target gene is PUMA, which encodes a BH3-only proapoptotic protein. Here we demonstrate that Puma deletion in the Eµ-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that ~75% of Eµ-Myc lymphomas naturally select against Puma protein expression. Furthermore, approximately 40% of primary human Burkitt lymphomas fail to express detectable levels of PUMA and in some tumors this is associated with DNA methylation. Burkitt lymphoma cell lines phenocopy the primary tumors with respect to DNA methylation and diminished PUMA expression, which can be reactivated following inhibition of DNA methyltransferases. These findings establish that PUMA is silenced in human malignancies, and they suggest PUMA as a target for the development of novel chemotherapeutics.

View Fulltext    |   Related Articles   |   Back
   
 
 
 
  Related Articles

No Article Found
 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility