Apoptosis to autophagy switch triggered by the MHC class III-encoded receptor for advanced glycation endproducts (RAGE).
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin gene superfamily, encoded within the major histocompatability complex class III region. Its multiple ligands include the high mobility group box 1 chromatin binding protein, HMGB1. Recently we reported that RAGE-HMGB1 critically regulates autophagy and apoptosis in pancreatic cancer cells in vivo and in vitro in response to chemotherapy. RAGE inhibits apoptosis ("programmed cell death") by a p53 transcription-independent pathway during the response to chemotherapeutic agents. RAGE sustains autophagy ("programmed cell survival") associated with decreased phosphorylation of the mammalian target of rapamycin (mTOR) and increased Beclin 1-Vps34 interaction. These findings provide insight into how autophagy- and apoptosis-crossregulatory molecules interact in response to cellular stress including tumor therapy.
Kang
Rui
R
The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Tang
Daolin
D
Loze
Michael T
MT
Zeh
Herbert J
HJ
D017209:Apoptosis; D001343:Autophagy; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008954:Models, Biological; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016159:Tumor Suppressor Protein p53