TY - JOUR
T1 - RACK1 depletion in the ribosome induces selective translation for non-canonical autophagy
AU - Kim, Hag Dong
AU - Kong, Eunbin
AU - Kim, Yongjoong
AU - Chang, Jin Soo
AU - Kim, Joon
N1 - Funding Information:
Acknowledgements. This work was supported by NRF-2013R1A1A2012052 and NRF-2015R1A2A1A05001823. MEF cells were gifted by Young J Oh (Department of Biology, Yonsei University College of Life Science and Biotechnology).
Funding Information:
This work was supported by NRF-2013R1A1A2012052 and NRF-2015R1A2A1A05001823. MEF cells were gifted by Young J Oh (Department of Biology, Yonsei University College of Life Science and Biotechnology).
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins. Therefore, we propose that the RACK1 depletion-induced autophagy is distinct from canonical autophagy. Finally, we confirm that cells expressing mutant RACK1 (RACK1R36D/K38E ) defective in ribosome binding showed the same result as RACK1-knockdown cells. Altogether, our data clearly show that the depletion of ribosomal RACK1 alters the capacity of the ribosome to translate specific mRNAs, resulting in selective translation of mRNAs of genes for non-canonical autophagy induction.
AB - RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins. Therefore, we propose that the RACK1 depletion-induced autophagy is distinct from canonical autophagy. Finally, we confirm that cells expressing mutant RACK1 (RACK1R36D/K38E ) defective in ribosome binding showed the same result as RACK1-knockdown cells. Altogether, our data clearly show that the depletion of ribosomal RACK1 alters the capacity of the ribosome to translate specific mRNAs, resulting in selective translation of mRNAs of genes for non-canonical autophagy induction.
UR - http://www.scopus.com/inward/record.url?scp=85042674182&partnerID=8YFLogxK
U2 - 10.1038/CDDIS.2017.204
DO - 10.1038/CDDIS.2017.204
M3 - Article
C2 - 28518135
AN - SCOPUS:85042674182
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 5
M1 - e2800
ER -
