Chen, B., Sun, Y., Niu, J., Jarugumilli, G. K. & Wu, X. Protein lipidation in cell signaling and diseases: function, regulation, and therapeutic opportunities. Cell Chem. Biol. 25, 817–831 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang, H. et al. Protein lipidation: occurrence, mechanisms, biological functions, and enabling technologies. Chem. Rev. 118, 919–988 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berndt, N., Hamilton, A. D. & Sebti, S. M. Targeting protein prenylation for cancer therapy. Nat. Rev. Cancer 11, 775–791 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meinnel, T., Dian, C. & Giglione, C. Myristoylation, an ancient protein modification mirroring eukaryogenesis and evolution. Trends Biochem. Sci. 45, 619–632 (2020).

Article  CAS  PubMed  Google Scholar 

Lanyon-Hogg, T., Faronato, M., Serwa, R. A. & Tate, E. W. Dynamic protein acylation: new substrates, mechanisms, and drug targets. Trends Biochem. Sci. 42, 566–581 (2017).

Article  CAS  PubMed  Google Scholar 

Tang, H. & Han, M. Fatty acids regulate germline sex determination through ACS-4-dependent myristoylation. Cell 169, 457–469.e13 (2017).

Article  CAS  PubMed  Google Scholar 

Lee, H. W. et al. A phase II trial of tipifarnib for patients with previously treated, metastatic urothelial carcinoma harboring HRAS mutations. Clin. Cancer Res. 26, 5113–5119 (2020).

Article  CAS  PubMed  Google Scholar 

Ho, A. L. et al. Tipifarnib in head and neck squamous cell carcinoma with HRAS mutations. J. Clin. Oncol. 39, 1856–1864 (2021). This study describes the clinical application of a farnesyltransferase inhibitor in HRAS-mutant cancers.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mariscal, J. et al. Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles. J. Extracell. Vesicles 9, 1764192 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Tohumeken, S. et al. Palmitoylated proteins on AML-derived extracellular vesicles promote myeloid-derived suppressor cell differentiation via TLR2/Akt/mTOR signaling. Cancer Res. 80, 3663–3676 (2020).

Article  CAS  PubMed  Google Scholar 

Clara, J. A., Monge, C., Yang, Y. & Takebe, N. Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update. Nat. Rev. Clin. Oncol. 17, 204–232 (2020).

Article  PubMed  Google Scholar 

Kallemeijn, W. W. et al. Validation and invalidation of chemical probes for the human N-myristoyltransferases. Cell Chem. Biol. 26, 892–900.e4 (2019). The study has used an NMT inhibitor and demonstrated that widely used legacy tool compounds have primarily or exclusively off-target effects.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, M. & Casey, P. J. Protein prenylation: unique fats make their mark on biology. Nat. Rev. Mol. Cell Biol. 17, 110–122 (2016).

Article  CAS  PubMed  Google Scholar 

Taylor, J. S., Reid, T. S., Terry, K. L., Casey, P. J. & Beese, L. S. Structure of mammalian protein geranylgeranyltransferase type-I. EMBO J. 22, 5963–5974 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Park, H. W., Boduluri, S. R., Moomaw, J. F., Casey, P. J. & Beese, L. S. Crystal structure of protein farnesyltransferase at 2.25 Ångstrom resolution. Science 275, 1800–1804 (1997).

Article  CAS  PubMed  Google Scholar 

Zverina, E. A., Lamphear, C. L., Wright, E. N. & Fierke, C. A. Recent advances in protein prenyltransferases: substrate identification, regulation, and disease interventions. Curr. Opin. Chem. Biol. 16, 544–552 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Storck, E. M. et al. Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics. Nat. Chem. 11, 552–561 (2019). This study provides evidence for the extent of alternative prenylation, and tools for dissecting farnesyltransferase and geranylgeranyl transferase substrates.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hampton, S. E., Dore, T. M. & Schmidt, W. K. Rce1: mechanism and inhibition. Crit. Rev. Biochem. Mol. Biol. 53, 157–174 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diver, M. M., Pedi, L., Koide, A., Koide, S. & Long, S. B. Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT. Nature 553, 526–529 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Manolaridis, I. et al. Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1. Nature 504, 301–305 (2013).

Article  CAS  PubMed  Google Scholar 

Recchi, C. & Seabra, M. C. Novel functions for Rab GTPases in multiple aspects of tumour progression. Biochem. Soc. Trans. 40, 1398–1403 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin, H. et al. Rab GTPases: central coordinators of membrane trafficking in cancer. Front. Cell Dev. Biol. 9, 648384 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Leung, K. F., Baron, R. & Seabra, M. C. Thematic review series: lipid posttranslational modifications. geranylgeranylation of Rab GTPases. J. Lipid Res. 47, 467–475 (2006).

Article  CAS  PubMed  Google Scholar 

Winter-Vann, A. M. & Casey, P. J. Post-prenylation-processing enzymes as new targets in oncogenesis. Nat. Rev. Cancer 5, 405–412 (2005).

Article  CAS  PubMed  Google Scholar 

Kuchay, S. et al. GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase. Nat. Struct. Mol. Biol. 26, 628–636 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shirakawa, R. et al. A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. EMBO J. 39, e104120 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boudreau, D. M., Yu, O. & Johnson, J. Statin use and cancer risk: a comprehensive review. Expert Opin. Drug Saf. 9, 603–621 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jung, D. & Bachmann, H. S. Regulation of protein prenylation. Biomed. Pharmacother. 164, 114915 (2023).

Article  CAS  PubMed  Google Scholar 

Brandt, A. C., Koehn, O. J. & Williams, C. L. SmgGDS: an emerging master regulator of prenylation and trafficking by small GTPases in the Ras and Rho families. Front. Mol. Biosci. 8, 685135 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Zhou, M. et al. VPS35 binds farnesylated N-Ras in the cytosol to regulate N-Ras trafficking. J. Cell Biol. 214, 445–458 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zimmermann, G. et al. Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling. Nature 497, 638–642 (2013).

Article  CAS  PubMed  Google Scholar 

Garcia-Mata, R., Boulter, E. & Burridge, K. The ‘invisible hand’: regulation of RHO GTPases by RHOGDIs. Nat. Rev. Mol. Cell Biol. 12, 493–504 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Losada de la Lastra, A., Hassan, S. & Tate, E. W. Deconvoluting the biology and druggability of protein lipidation using chemical proteomics. Curr. Opin. Chem. Biol. 60, 97–112 (2021).

Article  CAS  PubMed  Google Scholar 

Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J. & Der, C. J. Drugging the undruggable RAS: mission possible? Nat. Rev. Drug Discov. 13, 828–851 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prior, I. A., Hood, F. E. & Hartley, J. L. The frequency of Ras mutations in cancer. Cancer Res. 80, 2969–2974 (2020).

Article  CAS  PubMed  PubMed Central