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PreprintCited by 208Epigenetics and DNA MethylationCancer-related gene regulationCancer-related Molecular Pathways

Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily

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Steele-Perkins, George, Fang, Wei, Yang, Xiao-Hong, Van Gele, Mireille, Carling, Tobias, Gu, Jian, Buyse, Inge M., Fletcher, Jonathon A. +7 more·2001·Genes & Development
DOI 10.1101/gad.870101PMC PMC312773
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Abstract

The retinoblastoma protein-interacting zinc finger gene RIZ (PRDM2) is a member, by sequence homology, of a nuclear protein-methyltransferase (MTase) superfamily involved in chromatin-mediated gene expression. The gene produces two protein products, RIZ1 that contains a conserved MTase domain and RIZ2 that lacks the domain. RIZ1 gene expression is frequently silenced in human cancers, and the gene is also a common target of frameshift mutation in microsatellite-unstable cancers. We now report studies of mice with a targeted mutation in the RIZ1 locus. The mutation inactivates RIZ1 but not RIZ2. These RIZ1 mutant mice were viable and fertile but showed a high incidence of diffuse large B-cell lymphomas (DLBL) and a broad spectrum of unusual tumors. RIZ1 deficiency also accelerated tumorigenesis in p53 heterozygous mutant mice. Finally, several missense mutations of RIZ1 were found in human tumor tissues and cell lines; one of these was particularly common in human DLBL tumors. These missense mutations, as well as the previously described frameshift mutation, all mapped to the MTase functional domains. All abolished the capacity of RIZ1 to enhance estrogen receptor activation of transcription. These data suggest a direct link between tumor formation and the MTase domain of RIZ1 and describe for the first time a tumor susceptibility gene among methyltransferases.

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Rb can interact with other histone methyltransferases.

    “However, Rb can interact with other histone methyltransferases (Steele-Perkins et al., 2001)”

    From Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence (2003) · cites this paper as Steele-Perkins et al., 2001

    The paper’s introductory passage identifies RIZ as an Rb-binding protein in the PR/SET methyltransferase family. But the Discussion says direct methyltransferase activity remains to be established for RIZ1, and the paper does not establish that it is a histone methyltransferase. The Rb interaction is supported; the histone-methyltransferase characterization is not. (LLM, conf=0.88)

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Authors
Steele-Perkins, G., Fang, W., Yang, X.-H., Van Gele, M., Carling, T., Gu, J., Buyse, I. M., Fletcher, J. A., Liu, J., Bronson, R., Chadwick, R. B., de la Chapelle, A., Zhang, X.-K., Speleman, F., & Huang, S.
Affiliations
  • Cleveland Clinic (US)
  • Tufts University (US)
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2001-09-01
Volume
15
Issue
17
Pages
2250-2262
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.870101
PMC
PMC312773
OpenAlex
W2166083262
Cited by
208
References
52
Citations by year
2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 12 · 2016: 8 · 2015: 15 · 2014: 8 · 2013: 9 · 2012: 10
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders
  • Tobacco-Related Disease Research Program
  • National Institutes of Health (5r01ca076146-03)
  • National Cancer Institute (CA-76146, CA60988, R01CA060988)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
RIZ1, PRDM2, cancer susceptibility genes, diffuse large B-cell lymphoma, carcinogenesis, microsatellite instability, frameshift mutation, missense mutations
MeSH terms
Alleles, Amino Acid Sequence, Animals, Base Sequence, DNA Mutational Analysis, DNA-Binding Proteins, Multigene Family, Heterozygote, Humans, Immunoglobulin Heavy Chains, Karyotyping, Models, Genetic, Molecular Sequence Data, Mutation, Neoplasms, Nuclear Proteins, Protein Binding, Histone-Lysine N-Methyltransferase, Receptors, Estrogen, Time Factors, Transcription Factors, Tumor Cells, Cultured, Blotting, Southern, Blotting, Northern, Transcriptional Activation, Genes, p53, Retinoblastoma Protein, Mutagenesis, Site-Directed, Frameshift Mutation, Protein Structure, Tertiary, Microsatellite Repeats, Genetic Predisposition to Disease, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction, Mice

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