Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control
Journal
Nucleic Acids Research
ISSN
0305-1048
Date Issued
2022
Author(s)
Francisco Saavedra
Claudia Espinoza-Arratia
Nicolas W Martinez
Tatiana Cruces
Alejandra Loyola
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title>
<jats:p>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.</jats:p>
<jats:p>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.</jats:p>
Cite this document
Hormazabal, J., Saavedra, F., Espinoza-Arratia, C., Martinez, N. W., Cruces, T., Alfaro, I. E., & Loyola, A. (2022). Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control. Nucleic Acids Research, 50(4), 1875-1887. https://doi.org/10.1093/nar/gkab1296
Subjects
autophagy
;
chaperone-mediated autophagy
;
histones
;
lysosomes
;
quality control
;
calreticulin
;
chaperone
;
dna topoisomerase
;
glycoprotein
;
heat shock cognate protein 70
;
heat shock protein 90
;
histone chaperone asf1
;
histone h2a
;
histone h3
;
histone h4
;
immunoglobulin g
;
karyopherin
;
lysosome associated membrane protein 1
;
lysosome associated membrane protein 2a
;
nuclear autoantigenic sperm protein
;
nuclear protein
;
unclassified drug
;
voltage dependent anion channel
;
histone
;
animal cell
;
article
;
binding competition
;
chaperone-mediated autophagy
;
competitive binding assay
;
confocal microscopy
;
controlled study
;
genetic transfection
;
hela cell line
;
histone degradation
;
human
;
human cell
;
human cell culture
;
immunofluorescence assay
;
lysosome
;
nonhuman
;
protein degradation
;
protein expression
;
protein folding
;
protein homeostasis
;
protein localization
;
protein metabolism
;
protein misfolding
;
protein protein interaction
;
quality control
;
rat
;
western blotting
;
autophagy
;
metabolism
;
quality control