Details

Autor(en) / Beteiligte

• Hormazabal, Juan
• Saavedra, Francisco
• Espinoza-Arratia, Claudia
• Martinez, Nicolas W
• Cruces, Tatiana
• Alfaro, Iván E
• Loyola, Alejandra

Titel

Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Ist Teil von

• Nucleic acids research, 2022-02, Vol.50 (4), p.1875-1887

Ort / Verlag

England

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.