title: Global mitotic phosphorylation of C2H2 zinc finger protein linker peptides.
abstract: Cessation of transcriptional activity is a hallmark of cell division. Many biochemical pathways have been shown and proposed over the past few decades to explain the silence of this phase. In particular, many individual transcription factors have been shown to be inactivated by phosphorylation. In this report, we show the simultaneous phosphorylation and mitotic redistribution of a whole class of modified transcription factors. C(2)H(2) zinc finger proteins (ZFPs) represent the largest group of gene expression regulators in the human genome. Despite their diversity, C(2)H(2) ZFPs display striking conservation of small linker peptides joining their adjacent zinc finger modules. These linkers are critical for DNA binding activity. It has been proposed that conserved phosphorylation of these linker peptides could be a common mechanism for the inactivation of the DNA binding activity of C(2)H(2) ZFPs, during mitosis. Using a novel antibody, raised against the phosphorylated form of the most conserved linker peptide sequence, we are able to visualize the massive and simultaneous mitotic phosphorylation of hundreds of these proteins. We show that this wave of phosphorylation is tightly synchronized, starting in mid-prophase right after DNA condensation and before the breakdown of the nuclear envelope. This global phosphorylation is completely reversed in telophase. In addition, the exclusion of the phospho-linker signal from condensed DNA clearly demonstrates a common mechanism for the mitotic inactivation of C(2)H(2) ZFPs.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
authors.forename: Raed
authors.initials: R
authors.lastname: Rizkallah
authors.forename: Karen E
authors.initials: KE
authors.lastname: Alexander
authors.forename: Myra M
authors.initials: MM
authors.lastname: Hurt
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D010766:Phosphorylation; D012097:Repressor Proteins; D013692:Telophase; D050986:YY1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D004247:DNA