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SHR Neuro Krebs Kardio Lipid

Göbl, C; Morris, VK; van Dam, L; Visscher, M; Polderman, PE; Hartlmüller, C; de Ruiter, H; Hora, M; Liesinger, L; Birner-Gruenberger, R; Vos, HR; Reif, B; Madl, T; Dansen, TB.
Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A.
Redox Biol. 2020; 28: 101316-101316. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Birner-Grünberger Ruth
Liesinger Laura
Madl Tobias
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Abstract:
The tumor suppressor p16INK4A induces cell cycle arrest and senescence in response to oncogenic transformation and is therefore frequently lost in cancer. p16INK4A is also known to accumulate under conditions of oxidative stress. Thus, we hypothesized it could potentially be regulated by reversible oxidation of cysteines (redox signaling). Here we report that oxidation of the single cysteine in p16INK4A in human cells occurs under relatively mild oxidizing conditions and leads to disulfide-dependent dimerization. p16INK4A is an all α-helical protein, but we find that upon cysteine-dependent dimerization, p16INK4A undergoes a dramatic structural rearrangement and forms aggregates that have the typical features of amyloid fibrils, including binding of diagnostic dyes, presence of cross-β sheet structure, and typical dimensions found in electron microscopy. p16INK4A amyloid formation abolishes its function as a Cyclin Dependent Kinase 4/6 inhibitor. Collectively, these observations mechanistically link the cellular redox state to the inactivation of p16INK4A through the formation of amyloid fibrils. Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Find related publications in this database (Keywords)
Amyloids
Protein aggregation
Redox signaling
Cysteine oxidation
Structural biology
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