Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma.
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.
Niklinski
J
J
Department of Developmental Therapeutics, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, USA.
Claassen
G
G
Meyers
C
C
Gregory
M A
MA
Allegra
C J
CJ
Kaye
F J
FJ
Hann
S R
SR
Zajac-Kaye
M
M
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*
D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D014404:Tubulin