<div class="csl-bib-body">
<div class="csl-entry">Göbl, C., Morris, V. K., van Dam, L., Visscher, M., Polderman, P. E., Hartlmüller, C., de Ruiter, H., Hora, M., Liesinger, L., Birner-Grünberger, R., Vos, H. R., Reif, B., Madl, T., & Dansen, T. B. (2020). Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A. <i>Redox Biology</i>, <i>28</i>(101316), 101316. https://doi.org/10.1016/j.redox.2019.101316</div>
</div>
-
dc.identifier.issn
2213-2317
-
dc.identifier.uri
http://hdl.handle.net/20.500.12708/141697
-
dc.description.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.
en
dc.language.iso
en
-
dc.publisher
ELSEVIER
-
dc.relation.ispartof
Redox Biology
-
dc.subject
Biochemistry
-
dc.subject
Clinical Biochemistry
-
dc.subject
Organic Chemistry
-
dc.subject
Amyloids
-
dc.subject
Protein aggregation
-
dc.subject
Redox signaling
-
dc.subject
Cysteine oxidation
-
dc.subject
Structural biology
-
dc.title
Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A.
en
dc.type
Artikel
de
dc.type
Article
en
dc.description.startpage
101316
-
dc.type.category
Original Research Article
-
tuw.container.volume
28
-
tuw.container.issue
101316
-
tuw.journal.peerreviewed
true
-
tuw.peerreviewed
true
-
tuw.researchTopic.id
M6
-
tuw.researchTopic.name
Biological and Bioactive Materials
-
tuw.researchTopic.value
100
-
dcterms.isPartOf.title
Redox Biology
-
tuw.publication.orgunit
E164-01-3 - Forschungsgruppe Bioanalytik
-
tuw.publisher.doi
10.1016/j.redox.2019.101316
-
dc.identifier.eissn
2213-2317
-
dc.description.numberOfPages
1
-
wb.sci
true
-
wb.sciencebranch
Chemie
-
wb.sciencebranch
Biologie
-
wb.sciencebranch.oefos
1040
-
wb.sciencebranch.oefos
1060
-
wb.facultyfocus
Bioscience Technology
de
wb.facultyfocus
Bioscience Technology
en
wb.facultyfocus.faculty
E150
-
item.languageiso639-1
en
-
item.grantfulltext
restricted
-
item.openairecristype
http://purl.org/coar/resource_type/c_2df8fbb1
-
item.fulltext
no Fulltext
-
item.openairetype
research article
-
item.cerifentitytype
Publications
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.orcid
0000-0003-3950-0312
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164 - Institut für Chemische Technologien und Analytik