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.
The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Rui
R
Kang
Daolin
D
Tang
Michael T
MT
Loze
Herbert J
HJ
Zeh
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