RT Journal Article
SR Electronic
T1 An N-terminal–truncated isoform of FAM134B (FAM134B-2) regulates starvation-induced hepatic selective ER-phagy
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900340
DO 10.26508/lsa.201900340
VO 2
IS 3
A1 Kohno, Shohei
A1 Shiozaki, Yuji
A1 Keenan, Audrey L
A1 Miyazaki-Anzai, Shinobu
A1 Miyazaki, Makoto
YR 2019
UL http://www.life-science-alliance.org/content/2/3/e201900340.abstract
AB Autophagy is a conserved system that adapts to nutrient starvation, after which proteins and organelles are degraded to recycle amino acids in response to starvation. Recently, the ER was added to the list of targets of autophagic degradation. Autophagic degradation pathways of bulk ER and the specific proteins sorted through the ER are considered key mechanisms in maintaining ER homeostasis. Four ER-resident proteins (FAM134B, CCPG1, SEC62, and RTN3) have been identified as ER-resident cargo receptors, which contain LC3-interacting regions. In this study, we identified an N-terminal–truncated isoform of FAM134B (FAM134B-2) that contributes to starvation-induced ER-related autophagy. Hepatic FAM134B-2 but not full-length FAM134B (FAM134B-1) is expressed in a fed state. Starvation drastically induces FAM134B-2 but no other ER-resident cargo receptors through transcriptional activation by C/EBPβ. C/EBPβ overexpression increases FAM134B-2 recruitment into autophagosomes and lysosomal degradation. FAM134B-2 regulates lysosomal degradation of ER-retained secretory proteins such as ApoCIII. This study demonstrates that the C/EBPβ-FAM134B-2 axis regulates starvation-induced selective ER-phagy.