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Updated: Jun 22, 2026

Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions
Published on: May 28, 2017
Activation of alternative Jdp2 promoters and functional protein isoforms in T-cell lymphomas by retroviral insertion
Mads Heilskov Rasmussen1, Bruce Wang, Matthias Wabl
1Department of Molecular Biology, Aarhus University, Arhus, DK 8000, Denmark.
Abstract:
Retroviral insertional mutagenesis has been instrumental for the identification of genes important in cancer development. The molecular mechanisms involved in retroviral-mediated activation of proto-oncogenes influence the distribution of insertions within specific regions during tumorigenesis and hence may point to novel gene structures. From a retroviral tagging screen on tumors of 1767 SL3-3 MLV-infected BALB/c mice, intron 2 of the AP-1 repressor Jdp2 locus was found frequently targeted by proviruses resulting in upregulation of non-canonical RNA subspecies. We identified several promoter regions within 1000 bp upstream of exon 3 that allowed for the production of Jdp2 protein isoforms lacking the histone acetylase inhibitory domain INHAT present in canonical Jdp2. The novel Jdp2 isoforms localized to the nucleus and over-expression in murine fibroblast cells induced cell death similar to canonic Jdp2. When expressed in the context of oncogenic NRAS both full length Jdp2 and the shorter isoforms increased anchorage-independent growth. Our results demonstrate a biological function of Jdp2 lacking the INHAT domain and suggest a post-genomic application for the use of retroviral tagging data in identifying new gene products with a potential role in tumorigenesis.
Insights
Retroviral tagging identified novel Jdp2 protein isoforms lacking the INHAT domain. These isoforms contribute to cancer development by promoting cell growth and anchorage-independent growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Retroviral insertional mutagenesis is crucial for identifying cancer-driving genes.
- Understanding proto-oncogene activation mechanisms can reveal novel gene structures.
Purpose of the Study:
- To identify novel gene products involved in tumorigenesis using retroviral tagging.
- To investigate the function of newly identified Jdp2 protein isoforms.
Main Methods:
- A retroviral tagging screen was performed on tumors from SL3-3 MLV-infected mice.
- Analysis of proviral insertion sites and gene expression.
- Characterization of novel Jdp2 protein isoforms and their biological functions.
Main Results:
- Intron 2 of the Jdp2 locus was frequently targeted, leading to non-canonical RNA upregulation.
- Novel Jdp2 isoforms lacking the INHAT domain were identified.
- These isoforms promote cell death and enhance anchorage-independent growth in the context of oncogenic NRAS.
Conclusions:
- Jdp2 lacking the INHAT domain has a biological function in tumorigenesis.
- Retroviral tagging data can identify new gene products with roles in cancer.
- Novel Jdp2 isoforms represent potential therapeutic targets.
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