# Mechanisms elicited by type I interferons in cutaneous photocarcinogenesis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $323,400

## Abstract

ABSTRACT
Type I interferons (IFNs) are cytokines, that are important regulators of immune responses and are
downregulated in human cancers, including skin cancer, Solar ultraviolet (UV) radiation is a proven
environmental carcinogen, and exposure to solar radiation contributes to the high prevalence of skin cancer.
The carcinogenic effects of UV light can be attributed to the formation of cyclobutane pyrimidine dimers (CPD)
and errors in repair and replication of DNA. It is believed that type I IFNs reduce cellular proliferation and allow
DNA repair in various diseases. This suggests that type I IFNs may play a key role in repair of UVB induced
DNA damage. Our studies show that mice lacking the type I IFN receptor 1 (IFNAR1) had decreased repair of
UVB induced CPD in the skin and increased immunosuppression. Regulation of type I IFNs has been well
studied at the transcriptional level but there is a dearth of information on regulation at the post-transcriptional
level. K-homology type regulatory splicing protein (KSRP) has been shown to regulate the production of type I
IFNs, at the post-transcriptional level in response to viral infection, by promoting the decay of their mRNA. We
have found that KSRP inhibits the repair of CPD in mouse skin and is highly expressed in human skin tumors
compared to normal skin. We hypothesize that type I IFNs will repair UVB induced DNA damage and prevent
tumor development in mice. These type I IFN mediated processes will be regulated by KSRP. To test our
hypothesis, we will use mice, lacking IFNAR1, which is critical for signaling of type I IFNs, and mice lacking
KSRP. Using these unique mouse models, we will be able to (1) Determine the mechanisms by which type I
IFNs are produced after UVB induced DNA damage, the cell type that produces them, and the manner in
which they repair the CPD formed after exposure to UVB radiation; (2) Dissect the mechanism of regulation of
type I IFNs by KSRP, after UVB induced DNA damage; (3) Elucidate whether type I IFNs mediate development
of UVB induced skin tumors and whether KSRP contributes to their regulation in this process.

## Key facts

- **NIH application ID:** 10019328
- **Project number:** 5R01AR071157-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Nabiha Yusuf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $323,400
- **Award type:** 5
- **Project period:** 2016-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019328

## Citation

> US National Institutes of Health, RePORTER application 10019328, Mechanisms elicited by type I interferons in cutaneous photocarcinogenesis (5R01AR071157-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10019328. Licensed CC0.

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