title: Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma.
abstract: Somatic mutations at Thr-58 of c-Myc have been detected in Burkitt's lymphoma (BL) tumors and have been shown to affect the transforming potential of the Myc oncoprotein. In addition, the N-terminal domain of c-Myc has been shown to interact with microtubules in vivo, and the binding of c-Myc to alpha-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with alpha-tubulin. In addition, we show that wild-type c-Myc-alpha-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells.
authors.affiliation: Department of Developmental Therapeutics, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, USA.
authors.forename: J
authors.initials: J
authors.lastname: Niklinski
authors.forename: G
authors.initials: G
authors.lastname: Claassen
authors.forename: C
authors.initials: C
authors.lastname: Meyers
authors.forename: M A
authors.initials: MA
authors.lastname: Gregory
authors.forename: C J
authors.initials: CJ
authors.lastname: Allegra
authors.forename: F J
authors.initials: FJ
authors.lastname: Kaye
authors.forename: S R
authors.initials: SR
authors.lastname: Hann
authors.forename: M
authors.initials: M
authors.lastname: Zajac-Kaye
mesh_terms: D019943:Amino Acid Substitution; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D014404:Tubulin