TY - JOUR
T1 - Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control
AU - Hormazabal, Juan
AU - Saavedra, Francisco
AU - Espinoza-Arratia, Claudia
AU - Martinez, Nicolas W.
AU - Cruces, Tatiana
AU - Alfaro, Iván E.
AU - Loyola, Alejandra
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2022/2/28
Y1 - 2022/2/28
N2 - Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.
AB - Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.
UR - http://www.scopus.com/inward/record.url?scp=85125550849&partnerID=8YFLogxK
U2 - 10.1093/nar/gkab1296
DO - 10.1093/nar/gkab1296
M3 - Article
C2 - 35037039
AN - SCOPUS:85125550849
SN - 0305-1048
VL - 50
SP - 1875
EP - 1887
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 4
ER -