"Mechanisms of A1/Bfl-1 suppressed cell death"
People involved: Manuel Haschka, Andreas Villunger, Maja Sochalska and Selma Tuzlak.
Pro-survival Bcl-2 family proteins preserve mitochondrial integrity by sequestering either BH3-only protein members of the same family, or by neutralizing active Bax or Bak at the outer mitochondrial membrane. Inhibiting anti-apoptotic Bcl-2 homologs constitutes a new avenue for the treatment of cancer and autoimmunity (1). The mechanisms how anti-apoptotic A1/Bfl-1, a protein reported to mediate survival and maturation of early thymic precursors and myeloid cells blocks cell death remains uncertain and physiological consequences of loss of A1/Bfl-1-function await detailed investigation (2). Given its noted overexpression and proposed role in the pathogenesis of hematopoietic malignancies and their drug-resistance to novel therapeutics (e.g. BH3-mimetics), inhibiting A1/Bfl-1 function offers new therapeutic options (3). Understanding the consequences of A1/Bfl-1 loss-of-function and its molecular mode of action thereby constitute a prerequisite to validate the drug-target potential of this Bcl-2 homologue and shall be addressed within this DACH proposal.
Prof. Andreas Villunger, MSc, PhD Medical University InnsbruckKrebs_Team_Villunger Division of Developmental Immunology Biocenter Innrain 8082 A6020 Innsbruck AUSTRIA phone: 0043-512-9003-70380 fax: 0043-512-9003-70964 www.apoptosis.at