Data di Pubblicazione:
2022
Abstract:
PA28γ is a nuclear activator of the 20S proteasome that, unlike the 19S regulatory particle, stimulates hydrolysis of several
substrates in an ATP- and ubiquitin-independent manner and whose exact biological functions and molecular mechanism
of action still remain elusive. In an effort to shed light on these important issues, we investigated the stimulatory effect of
PA28γ on the hydrolysis of different fluorogenic peptides and folded or denatured full-length proteins by the 20S proteasome.
Importantly, PA28γ was found to dramatically enhance breakdown rates by 20S proteasomes of several naturally or artificially
unstructured proteins, but not of their native, folded counterparts. Furthermore, these data were corroborated by experiments
in cell lines with a nucleus-tagged myelin basic protein. Finally, mass spectrometry analysis of the products generated during
proteasomal degradation of two proteins demonstrated that PA28γ does not increase, but rather decreases, the variability of
peptides that are potentially suitable for MHC class I antigen presentation. These unexpected findings indicate that global
stimulation of the degradation of unfolded proteins may represent a more general feature of PA28γ and suggests that this
proteasomal activator might play a broader role in the pathway of protein degradation than previously believed.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
Proteasome activator, Proteasome gate, Protein degradation, ATP-independent proteolysis, Intrinsically disordered proteins (IDP), PA28αβ, PSME 3
Elenco autori:
Jean-Yves Alejandro Frayssinhes, Fulvia Cerruti, Justine Laulin, Angela Cattaneo, Angela Bachi, Sebastien Apcher, Olivier Coux, Paolo Cascio
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