Constitutive c-Myb amino-terminal phosphorylation and DNA binding activity uncoupled during entry and passage through the cell cycle

Oncogene
A CuresRobert G Ramsay

Abstract

The c-myb gene encodes a transcription factor that is central to hematopoietic cell growth. Phosphorylation of c-Myb by casein kinase 2 (CK2) at serines 11 and 12 has been variously implicated in the regulation of DNA binding. However, it is unclear when c-Myb phosphorylation at serines 11 and 12 occurs during the cell cycle and how this is regulated. We generated specific antisera that recognize phosphoserines 11 and 12 of c-Myb. C-Myb protein levels, extent of CK2 phosphorylation and DNA binding were then monitored following mitogenic stimulus and passage through the cell cycle in normal peripheral T-cells and the T leukemia cell line CCRF-CEM. We found that endogenous c-Myb is constitutively phosphorylated at serines 11 and 12. The amount of phosphorylated c-Myb correlates with DNA binding activity in cycling CEM cells but not upon entry of T-cells into the cell cycle. Exogenous expression of c-Myb with substitutions of serines 11 and 12 with glutamic acid or alanine had no effect on the transactivation of a c-Myb responsive reporter. These data strongly suggest that c-Myb is constitutively phosphorylated on serines 11 and 12 by CK2 or like activity and is not regulated during the cell cycle.

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Citations

Sep 16, 2003·Blood Cells, Molecules & Diseases·Scott A Ness
Jun 25, 2008·Nature Reviews. Cancer·Robert G Ramsay, Thomas J Gonda
Sep 10, 2008·Mutation Research·Roopam Singh, Louise M Winn
Nov 17, 2007·Blood Cells, Molecules & Diseases·Elisabetta Pani, Stefano Ferrari
Aug 7, 2002·Biochemical and Biophysical Research Communications·Mary E CostantinoDouglas S Darling
Nov 16, 2001·AIDS Research and Human Retroviruses·M J ChurchillN J Deacon
Nov 14, 2013·Cancer Research·Pingyan ChengDmitry Gabrilovich
Apr 22, 2018·Journal of Proteome Research·Brittany N PeaseDebopam Chakrabarti

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