D154Q Mutation does not Alter KRAS Dimerization.

Cell Line, Tumor Dimerization Humans Immunoprecipitation Mutation Neoplasms / therapy Proto-Oncogene Proteins p21(ras) / chemistry Signal Transduction
Cancer therapeutics KRAS MaMTH Oncogenic signalling SIMPL co-immunoprecipitation dimerization

Journal

Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R

Informations de publication

Date de publication:
30 01 2022
Historique:
received: 21 10 2021
revised: 30 11 2021
accepted: 01 12 2021
pubmed: 14 12 2021
medline: 5 2 2022
entrez: 13 12 2021
Statut: ppublish

Résumé

KRAS is one of the most frequently mutated oncogenes in human cancers. Despite nearly 40 years of research, KRAS remains largely undruggable, in part due to an incomplete understanding of its biology. Recently, KRAS dimerization was discovered to play an important role in its signalling function. The KRAS D154Q mutant was described as a dimer-deficient variant that can be used to study the effect of dimerization in KRAS oncogenicity. However, we show here that KRAS D154Q homo- and heterodimerized with KRAS WT using three separate protein-protein interaction assays, and that oncogenic KRAS dimerization was not negatively impacted by the presence of a secondary D154Q mutation. In conclusion, we advise caution in using this variant to study the purpose of dimerization in KRAS oncogenic behaviour.

Identifiants

DOI: 10.1016/j.jmb.2021.167392 PMID: 34896362
pubmed: 34896362
pii: S0022-2836(21)00629-X
doi: 10.1016/j.jmb.2021.167392
pii:
doi:

Substances chimiques

KRAS protein, human 0
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

167392

Subventions

Organisme : CIHR
ID : 420989
Pays : Canada

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Ingrid Grozavu (I)

Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Sarah Stuart (S)

Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Anna Lyakisheva (A)

Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Zhong Yao (Z)

Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Shivanthy Pathmanathan (S)

Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Michael Ohh (M)

Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Igor Stagljar (I)

Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Mediterranean Institute for Life Sciences (MedILS), Split, Croatia; School of Medicine, University of Split, Croatia. Electronic address: igor.stagljar@utoronto.ca.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Métabolisme › Dimérisation › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunoprécipitation › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Tumeurs › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › D154Q Mutation does not Alter KRAS Dimerization.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › D154Q Mutation does not Alter KRAS Dimerization.