title: Potential role of tubulin tyrosine ligase-like enzymes in tumorigenesis and cancer cell resistance.
abstract: Polyglutamylation of tubulin and other non-tubulin substrates is a reversible posttranslational modification brought about by tubulin tyrosine-like ligases. Altered polyglutamylation is linked to tumorigenesis and resistance to chemotherapeutic drugs that target the microtubule, and therefore is a potential pharmacological target in cancer therapy. Despite the large amount of research focused on the development of anticancer agents, only a small number of well-characterized inhibitors of polyglutamylases have been identified, including the phosphinic acid-based inhibitors of Ttll7. In this minireview, we summarize the role of polyglutamylation in cancer, and draw attention to the largely unexplored area of polyglutamylase inhibition in the treatment of cancer.
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 5, 775 15 Olomouc, Czech Republic. Electronic address: viswanath.das@upol.cz.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Das
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kanakkanthara.arun@mayo.edu.
authors.forename: Arun
authors.initials: A
authors.lastname: Kanakkanthara
authors.affiliation: Matakina Technology Ltd, PO Box 24404, Manners Street Central, Wellington, New Zealand. Electronic address: ariane.chan@volparasolutions.com.
authors.forename: Ariane
authors.initials: A
authors.lastname: Chan
authors.affiliation: School of Biological Sciences and Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington, New Zealand. Electronic address: john.h.miller@vuw.ac.nz.
authors.forename: John H
authors.initials: JH
authors.lastname: Miller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D063646:Carcinogenesis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; C039520:tyrosine-tubulin; D014443:Tyrosine; D010453:Peptide Synthases; C112698:tubulin polyglutamylase
keywords: Cancer resistance; Microtubule; Polyglutamylation; Polyglutamylation inhibitors; Tumorigenesis