Disease relevance of HHO1

• Their removal in vitro allowed expression of the gene, designated PfPK5, in Escherichia coli, the resulting product having kinase activity against casein and histone H1 [1].
• In addition, comparison of the different inhibitory patterns obtained using histone H1 or GST (glutathione S-transferase)-pRb (retinoblastoma protein) fusion protein as substrate (the latter of which recognizes both the docking site and the catalytic site of Cdk2-cyclin A) offers interesting suggestions for the inhibitory mechanism of Sic1 [2].

High impact information on HHO1

• This factor has been identified in all eukaryotic cells, and in vitro histone H1 is the preferred substrate for phosphorylation [3].
• The triple-disrupted cells were arrested late in the mitotic (M) phase, which was accompanied by an accumulation of cells with divided chromosomes and sustained histone H1 kinase activity [4].
• Mutants were not defective, however, in their ability to activate Cdc28 kinase as assayed in vitro on the substrate histone H1 [5].
• SirT1 interacts with and deacetylates histone H1 at lysine 26 [6].
• However, disruption of HHO1 results in no significant changes in the phenotypes examined thus far [7].

Biological context of HHO1

• We also considered the possibility that HHO1 was involved in forming the heterochromatin at telomeres [8].
• Thus, the yeast histone H1-like gene appears to have no role in gene activation at a distance or in silencing under the conditions tested [8].
• Sequencing of the yeast genome has led to the identification of a putative histone H1 gene [9].
• Thus, our data demonstrate that removal of yeast histone H1 only results in decreased gene expression [9].
• Histone H1 expressed in Saccharomyces cerevisiae binds to chromatin and affects survival, growth, transcription, and plasmid stability but does not change nucleosomal spacing [10].

Anatomical context of HHO1

• FT210 cells and the parent wild-type FM3A cell line each possess at least three distinct histone H1 kinases [11].
• A cdc2-like kinase phosphorylates histone H1 in the amitotic macronucleus of Tetrahymena [12].
• The cell cycle of Fucus zygotes presented the other main features of a somatic cell cycle, such as a functional spindle assembly checkpoint that targets CDKs and the regulation of the early synthesis of two PSTAIRE CDKs, p32 and p34, and the associated histone H1 kinase activity as well as the regulation of CDKs by tyrosine phosphorylation [13].
• The inhibition of the mitotic kinases leads to a reduction in the histone H1 and H3 mitotic-associated phosphorylations, chromosome decondensation and nuclear membrane reformation [14].
• Myelin basic protein was identified as an excellent in vitro substrate, whereas histone H1 was only poorly phosphorylated [15].

Associations of HHO1 with chemical compounds

• In this report, we demonstrate that Cdc7 immune complexes are capable of phosphorylating mammalian histone H1 on serine and/or threonine residues [16].
• A glutathione S-transferase-G1 cyclin chimera (GST-Cln2p) efficiently binds to and activates Cdc28p as a histone H1 kinase [17].
• Immunoprecipitates with the anti-Cak1At antibody phosphorylated human CDK2 at the threonine residue (T160) within the T-loop and activated its activity to phosphorylate histone H1 [18].
• KFR1, a mitogen-activated protein (MAP) kinase identified in the African trypanosome, Trypanosoma brucei, is a serine protein kinase capable of phosphorylating the serine residues in histone H-1, myelin basic protein, and beta-casein [19].
• Depletion of histidine-tagged CRK3 from L. mexicana cell extracts, by Ni-nitrilotriacetic acid agarose selection, reduced histone H1 kinase activity binding to p13(suc1) [20].

Regulatory relationships of HHO1

• To test these hypotheses, a gene coding for a sea urchin histone H1 was expressed from the inducible GAL1 promoter in Saccharomyces cerevisiae by use of a YEp vector for high expression levels (strain YCL7) and a centromere vector for low expression levels (strain YCL1) [10].
• The subunits of histone H1 kinase have now been shown to be cyclins and the p34CDC2 kinase product of the cell cycle control gene CDC2 [21].
• In vitro histone H1 kinase assays and anti-phosphotyrosine Western Blotting confirmed the in vivo activating dephosphorylation of starfish CDK1-cyclinB by recombinant O. tauri Cdc25 [22].

Other interactions of HHO1

• Overexpression of a heterologous histone H1 from sea urchin showed an overall inhibition of gene activation by the GAL1 promoter, whereas overexpression of the yeast histone H1 had no effect [8].
• Also, the expression of A1, ALPHA2 or SUC2 genes, all of which are known to be responsive to an altered chromatin structure, was unchanged in HHO1 knockout or HHO1-overexpressing strains when compared to wild-type cells [8].
• Cln2 immunoprecipitated from cdc28-csr1 cells was completely defective in histone H1 kinase activity, due to defects in Cdc28 binding and activation by Cln2 [23].
• TPK2-HA-wt phosphorylated a peptide from Histone H1, proving that TPK2 is a functional kinase [24].

Analytical, diagnostic and therapeutic context of HHO1

• Localization of HHO1p in the chromatin, using an immunoprecipitation technique, showed preferential HHO1p binding to rDNA sequences [25].
• We have characterized the effects of a conditionally dicentric chromosome on the cell division cycle by using microscopy, flow cytometry, and an assay for histone H1 kinase activity [26].

References