# CARD-only protein regulation of cytosolic Pattern Recognition Receptor signaling

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $578,794

## Abstract

Although, acute inflammatory responses have a protective role in innate immunity and host defense,
dysregulation and failure to properly resolve these responses cause inflammatory and infectious disease.
Several key cytosolic pattern recognition receptors signal through proteins containing the Caspase recruitment
domain (CARD), which is a protein-protein interaction domain, leading to inflammasome and NF-kB activation,
and inflammatory cytokine and type I interferon (IFN) production. However, the molecular mechanisms by
which these pathways are controlled to limit excessive and detrimental inflammatory responses, are largely
unknown.
 Three small proteins containing only a CARD, which are referred to as CARD-only proteins (COPs)
exist in humans, but like the related PYRIN domain-only proteins (POPs), are lacking from mice, which
supports the notion that these inflammatory responses require a tight control in particular in humans. COPs
have been identified over a decade ago, but except of a few initial overexpression studies, nothing is known
about the precise role of these proteins. We demonstrated key inflammasome regulatory activities of the three
POPs encoded in humans using a comprehensive analysis in humans and transgenic mice, and we
hypothesize that similarly, COPs will have an important role in regulating inflammatory responses and our
preliminary data indicate that COPs have a broader role than POPs by targeting several key pattern
recognition receptors. The research outlined in this proposal is geared to define the precise role of each COP
in macrophages during infection and inflammation, using a comprehensive analysis combining biochemical,
molecular and genetic approaches. We will also define their role during inflammatory and infectious disease,
using novel generated transgenic mice for all three COPs.
 We expect that our research will uncover novel molecular control mechanisms that prevent
inappropriate inflammation and will therefore be highly significant and relevant for better understanding innate
immunity and inflammatory disease and for providing the basis for developing novel therapies to benefit
patients and will therefore positively affect human health.

## Key facts

- **NIH application ID:** 9959337
- **Project number:** 5R01AI140702-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Andrea Dorfleutner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $578,794
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959337

## Citation

> US National Institutes of Health, RePORTER application 9959337, CARD-only protein regulation of cytosolic Pattern Recognition Receptor signaling (5R01AI140702-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9959337. Licensed CC0.

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