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Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies

Palmitoylation is a critical posttranslational modification that enables the cellular membrane localization and subsequent activation of RAS proteins, including HRAS, KRAS, and NRAS. However, the molecular mechanism that regulates RAS palmitoylation in malignant diseases remains unclear. In this iss...

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Detalles Bibliográficos
Autores principales: Yu, Fang, Qian, Zhijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266771/
https://www.ncbi.nlm.nih.gov/pubmed/37317974
http://dx.doi.org/10.1172/JCI171104
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author Yu, Fang
Qian, Zhijian
author_facet Yu, Fang
Qian, Zhijian
author_sort Yu, Fang
collection PubMed
description Palmitoylation is a critical posttranslational modification that enables the cellular membrane localization and subsequent activation of RAS proteins, including HRAS, KRAS, and NRAS. However, the molecular mechanism that regulates RAS palmitoylation in malignant diseases remains unclear. In this issue of the JCI, Ren, Xing, and authors shed light on this topic and revealed how upregulation of RAB27B, as a consequence of CBL loss and Janus kinase 2 (JAK2) activation, contributes to leukemogenesis. The authors found that RAB27B mediated NRAS palmitoylation and plasma membrane localization by recruiting ZDHHC9. The findings suggest that targeting RAB27B could provide a promising therapeutic strategy for NRAS-driven cancers.
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spelling pubmed-102667712023-06-15 Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies Yu, Fang Qian, Zhijian J Clin Invest Commentary Palmitoylation is a critical posttranslational modification that enables the cellular membrane localization and subsequent activation of RAS proteins, including HRAS, KRAS, and NRAS. However, the molecular mechanism that regulates RAS palmitoylation in malignant diseases remains unclear. In this issue of the JCI, Ren, Xing, and authors shed light on this topic and revealed how upregulation of RAB27B, as a consequence of CBL loss and Janus kinase 2 (JAK2) activation, contributes to leukemogenesis. The authors found that RAB27B mediated NRAS palmitoylation and plasma membrane localization by recruiting ZDHHC9. The findings suggest that targeting RAB27B could provide a promising therapeutic strategy for NRAS-driven cancers. American Society for Clinical Investigation 2023-06-15 /pmc/articles/PMC10266771/ /pubmed/37317974 http://dx.doi.org/10.1172/JCI171104 Text en © 2023 Yu, et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Commentary
Yu, Fang
Qian, Zhijian
Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title_full Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title_fullStr Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title_full_unstemmed Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title_short Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies
title_sort mechanisms for regulation of ras palmitoylation and plasma membrane trafficking in hematopoietic malignancies
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266771/
https://www.ncbi.nlm.nih.gov/pubmed/37317974
http://dx.doi.org/10.1172/JCI171104
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