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Distinct modulatory...
Distinct modulatory role of RNA in the aggregation of the tumor suppressor protein p53 core domain.
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- Kovachev, Petar Stefanov (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Banerjee, Debapriya (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Rangel, Luciana Pereira (författare)
- Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil.
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- Eriksson, Jonny (författare)
- Uppsala universitet,Analytisk kemi
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- Pedrote, Murilo M (författare)
- Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo de Meis, Inst Nacl Ciencia Tecnol Biol Estrutural & Bioima, BR-21941902 Rio De Janeiro, Brazil.
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- Martins-Dinis, Mafalda Maria D C (författare)
- Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo de Meis, Inst Nacl Ciencia Tecnol Biol Estrutural & Bioima, BR-21941902 Rio De Janeiro, Brazil.
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- Edwards, Katarina (författare)
- Uppsala universitet,Analytisk kemi,Edwards grupp
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- Cordeiro, Yraima (författare)
- Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil.
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- Silva, Jerson L (författare)
- Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo de Meis, Inst Nacl Ciencia Tecnol Biol Estrutural & Bioima, BR-21941902 Rio De Janeiro, Brazil.
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- Sanyal, Suparna (författare)
- Uppsala universitet,Struktur- och molekylärbiologi
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(creator_code:org_t)
- American Society for Biochemistry and Molecular Biology, 2017
- 2017
- Engelska.
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 292:22, s. 9345-9357
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Inactivation of the tumor suppressor protein p53 by mutagenesis, chemical modification, protein-protein interaction, or aggregation has been associated with different human cancers. Although DNA is the typical substrate of p53, numerous studies have reported p53 interactions with RNA. Here, we have examined the effects of RNA of varied sequence, length, and origin on the mechanism of aggregation of the core domain of p53 (p53C) using light scattering, intrinsic fluorescence, transmission electron microscopy, thioflavin-T binding, seeding, and immunoblot assays. Our results are the first to demonstrate that RNA can modulate the aggregation of p53C and full-length p53. We found bimodal behavior of RNA in p53C aggregation. A low RNA:protein ratio (∼1:50) facilitates the accumulation of large amorphous aggregates of p53C. By contrast, at a high RNA:protein ratio (≥1:8), the amorphous aggregation of p53C is clearly suppressed. Instead, amyloid p53C oligomers are formed that can act as seeds nucleating de novo aggregation of p53C. We propose that structured RNAs prevent p53C aggregation through surface interaction and play a significant role in the regulation of the tumor suppressor protein.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- RNA
- amyloid
- domain V of 23S rRNA
- fluorescence
- kinetics
- p53
- p53C
- prion
- protein aggregation
- protein folding
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Kovachev, Petar ...
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Banerjee, Debapr ...
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Rangel, Luciana ...
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Eriksson, Jonny
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Pedrote, Murilo ...
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Martins-Dinis, M ...
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visa fler...
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Edwards, Katarin ...
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Cordeiro, Yraima
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Silva, Jerson L
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Sanyal, Suparna
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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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Journal of Biolo ...
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Uppsala universitet