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 lympho ma (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 s hown to interact with microtubules in vivo, and the binding of c-Myc to alp ha-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutatio n at Thr-58 from BL cell lines have increased stability and are constitutiv ely hyperphosphorylated, which disrupts the in vivo interaction of c-Myc wi th alpha-tubulin. In addition, we show that wild-type c-Myc-alpha-tubulin i nteractions are also disrupted during a transient mitosis-specific hyperpho sphorylation of c-Myc, which resembles the constitutive hyperphosphorylatio n pattern of Thr-58 in BL cells.