AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH

作者：Liiv Ingrid^*; Haljasorg Uku; Kisand Kai; Maslovskaja Julia; Laan Martti; Peterson Paert

来源：Biochemical and Biophysical Research Communications, 2012, 423(1): 32-37.

DOI：10.1016/j.bbrc.2012.05.057

• AIRE
• CARD domain
• Apoptosis
• GAPDH

AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells. Recent data have shown that AIRE can also induce apoptosis, which may be linked to cross-presentation of these self-antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We show that the HSR/CARD domain in AIRE together with a nuclear localization signal is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3-phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE-induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells.

• 出版日期2012-6-22