Atypical BH3-domains of BNIP3 and BNIP3L lead to autophagy in hypoxia.
Normal and tumor cells subjected to a hypoxic microenvironment show evidence of autophagy. We hypothesize that cells will sense hypoxia as a warning signal to upcoming drastic microenvironmental conditions and that autophagy, acting as a survival mechanism, will provide time for cells to adapt. This work demonstrates for the first time that the atypical BH3-domain of BNIP3 and BNIP3L, two HIF-target genes, can compete with Beclin 1-Bcl-2 and Beclin 1-Bcl-X(L) complexes, releasing Beclin 1 from the complex and then enhancing autophagy. We thus revealed a new role for BH3-only proteins in the cellular response to hypoxia.
Mazure
Nathalie M
NM
Institute of Developmental Biology and Cancer, CNRS, Nice, France.
Pouysségur
Jacques
J
D001343:Autophagy; D015687:Cell Hypoxia; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins