A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains.
Many nuclear proteins are inactivated during mitotic entry, presumably as a prerequisite to chromatin condensation and cell division. C2H2 zinc fingers define the largest transcription factor family in the human proteome. The linker separating finger motifs is highly conserved and resembles TGEKP in more than 5000 occurrences. However, the reason for this conservation is not fully understood. We demonstrate that all three linkers in the DNA-binding domain of Ikaros are phosphorylated during mitosis. Phosphomimetic substitutions abolished DNA-binding and pericentromeric localization. A linker within Sp1 was also phosphorylated, suggesting that linker phosphorylation provides a global mechanism for inactivation of the C2H2 family.
Dovat
Sinisa
S
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, California 90095, USA.
Ronni
Tapani
T
Russell
Dana
D
Ferrini
Roger
R
Cobb
Bradley S
BS
Smale
Stephen T
ST
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D051740:Ikaros Transcription Factor; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor