The dynamic nature of the K-Ras/calmodulin complex can be altered by oncogenic mutations.


Journal

Current opinion in structural biology
ISSN: 1879-033X
Titre abrégé: Curr Opin Struct Biol
Pays: England
ID NLM: 9107784

Informations de publication

Date de publication:
12 2021
Historique:
received: 02 04 2021
revised: 03 06 2021
accepted: 17 06 2021
pubmed: 27 7 2021
medline: 15 12 2021
entrez: 26 7 2021
Statut: ppublish

Résumé

Oncogenic mutant K-Ras promotes cancer cell proliferation, migration, invasion, and survival by assembling signaling complexes. To date, the functional and structural roles of K-Ras mutations within these complexes are incompletely understood despite their mechanistic and therapeutic significance. Here, we review recent advances in understanding specific binding between K-Ras and the calcium sensor calmodulin. This interaction positively and negatively regulates diverse functions of K-Ras in cancer, suggesting flexibility in K-Ras/calmodulin complex formation. Also, structural data suggest that oncogenic K-Ras likely samples several conformational states, influencing its distinct assemblies with calmodulin and with other proteins. Understanding how K-Ras interacts with calmodulin and with other partners is essential to discovering novel inhibitors of K-Ras in cancer.

Identifiants

pubmed: 34311289
pii: S0959-440X(21)00092-0
doi: 10.1016/j.sbi.2021.06.008
pii:
doi:

Substances chimiques

Calmodulin 0
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2
Calcium SY7Q814VUP

Types de publication

Journal Article Research Support, N.I.H., Intramural Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

164-170

Subventions

Organisme : NCI NIH HHS
ID : R01 CA188427
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States

Informations de copyright

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

Déclaration de conflit d'intérêts

Conflict of interest statement Nothing declared.

Auteurs

Hazem Abdelkarim (H)

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Nicholas Leschinsky (N)

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Hyunbum Jang (H)

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Laboratory of Cancer Immunometabolism, National Cancer Institute, Frederick, MD, 21702, USA.

Avik Banerjee (A)

Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.

Ruth Nussinov (R)

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Laboratory of Cancer Immunometabolism, National Cancer Institute, Frederick, MD, 21702, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.

Vadim Gaponenko (V)

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, 60607, USA. Electronic address: vadimg@uic.edu.

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Classifications MeSH