Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation.
Pubmed ID: 29239724 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A commercial antibody supplier and provider of various services.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis monoclonal targets Syntaxin 6 (C34B2) Rabbit mAb
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Raf-B (C-19)
View all literature mentionsThis polyclonal targets A-Raf (C-20)
View all literature mentionsThis polyclonal targets KRAS
View all literature mentionsThis polyclonal targets Transferrin Receptor antibody
View all literature mentionsThis monoclonal targets Human Sirt1, aa 508-616
View all literature mentionsThis unknown targets RAS-Related protein Ral-A
View all literature mentionsThis monoclonal targets Rat v-H-Ras Agarose Clone Y13-259
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis monoclonal targets Syntaxin 6 (C34B2) Rabbit mAb
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Raf-B (C-19)
View all literature mentionsThis polyclonal targets A-Raf (C-20)
View all literature mentionsThis polyclonal targets KRAS
View all literature mentionsThis polyclonal targets Transferrin Receptor antibody
View all literature mentionsThis monoclonal targets Human Sirt1, aa 508-616
View all literature mentionsThis unknown targets RAS-Related protein Ral-A
View all literature mentionsThis monoclonal targets Rat v-H-Ras Agarose Clone Y13-259
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions