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Molecular and Cellular Biology, July 2000, p. 5276-5284, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Disruption of Myc-Tubulin Interaction by Hyperphosphorylation of c-Myc during Mitosis or by Constitutive Hyperphosphorylation of Mutant c-Myc in Burkitt's Lymphoma

Jacek Niklinski,1,dagger Gisela Claassen,2 Cheryl Meyers,1 Mark A. Gregory,2 Carmen J. Allegra,1 Frederic J. Kaye,3 Stephen R. Hann,2 and Maria Zajac-Kaye1,*

Department of Developmental Therapeutics1 and Department of Genetics,3 Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, and Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-21752

Received 31 January 2000/Returned for modification 15 March 2000/Accepted 12 April 2000

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.


* Corresponding author. Mailing address: NCI-Navy Oncology Branch, Bldg. 8, R 5101, Bethesda, MD 20889. Phone: (301) 402-0082. Fax: (301) 480-0977. E-mail: Kayem{at}exchange.nih.gov.

dagger Present address: Department of Thoracic Surgery, Medical School, Bialystok, Poland.


Molecular and Cellular Biology, July 2000, p. 5276-5284, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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