ArticleMolecular and cellular biology2001
HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 124 citations in OpenAlex.
- HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging.Research square · 2026Article
- Differential control of both cell cycle-regulated and quantitative histone mRNA expression bybioRxiv : the preprint server for biology · 2026Article
- Histone chaperone HIRA, promyelocytic leukemia protein, and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.Molecular cell · 2024Article
- HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.Experimental & molecular medicine · 2024Review
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- Inhibition of p90RSK Ameliorates PDGF-BB-Mediated Phenotypic Change of Vascular Smooth Muscle Cell and Subsequent Hyperplasia of Neointima.International journal of molecular sciences · 2023Article
- Article
- New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Dynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis.Frontiers in oncology · 2021Review
- Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability.Frontiers in cell and developmental biology · 2021Review
- Two HIRA-dependent pathways mediate H3.3 de novo deposition and recycling during transcription.Nature structural & molecular biology · 2020Article
- Article
- In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?Journal of neurodevelopmental disorders · 2019Review
- The histone chaperone HIRA promotes the induction of host innate immune defences in response to HSV-1 infection.PLoS pathogens · 2019Article
- Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.Nature communications · 2018Article
- Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity.Nucleic acids research · 2017Article
- Structural prediction of the interaction of the tumor suppressor p27BMC bioinformatics · 2017Article
- Fluvastatin inhibits AGE-induced cell proliferation and migration via an ERK5-dependent Nrf2 pathway in vascular smooth muscle cells.PloS one · 2017Article
- Differential regulation of the histone chaperone HIRA during muscle cell differentiation by a phosphorylation switch.Experimental & molecular medicine · 2016Article
- Cardiomyocyte-specific conditional knockout of the histone chaperone HIRA in mice results in hypertrophy, sarcolemmal damage and focal replacement fibrosis.Disease models & mechanisms · 2016Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Substrates of cyclin-cdk2 kinases contain two distinct primary sequence motifs: a cyclin-binding RXL motif and one or more phosphoacceptor sites (consensus S/TPXK/R or S/TP). To identify novel cyclin-cdk2 substrates, we searched the database for proteins containing both of these motifs. One such protein is human HIRA, the homologue of two cell cycle-regulated repressors of histone gene expression in Saccharomyces cerevisiae, Hir1p and Hir2p. Here we demonstrate that human HIRA is an in vivo substrate of a cyclin-cdk2 kinase. First, HIRA bound to and was phosphorylated by cyclin A- and E-cdk2 in vitro in an RXL-dependent manner. Second, HIRA was phosphorylated in vivo on two consensus cyclin-cdk2 phosphoacceptor sites and at least one of these, threonine 555, was phosphorylated by cyclin A-cdk2 in vitro. Third, phosphorylation of HIRA in vivo was blocked by cyclin-cdk2 inhibitor p21(cip1). Fourth, HIRA became phosphorylated on threonine 555 in S phase when cyclin-cdk2 kinases are active. Fifth, HIRA was localized preferentially to the nucleus, where active cyclin A- and E-cdk2 are located. Finally, ectopic expression of HIRA in cells caused arrest in S phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.