negative regulation of cytoplasmic pattern recognition receptor signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the series of a cytoplasmic pattern recognition receptor signaling pathway. [GOC:bf, GOC:jl]

Negative regulation of cytoplasmic pattern recognition receptor signaling pathway involves a complex interplay of molecular mechanisms that dampen and fine-tune the cellular response to pathogen-associated molecular patterns (PAMPs) detected in the cytoplasm. This intricate process ensures appropriate immune activation, preventing excessive inflammation and potentially harmful autoimmunity.

Key steps in this process include:

1. **Receptor Deactivation:** Pattern recognition receptors (PRRs) like NLRs and RIG-I-like receptors (RLRs) sense PAMPs and trigger downstream signaling cascades. Once activated, these receptors can be inactivated through various mechanisms, such as:
* **Ubiquitination and Degradation:** PRRs can be targeted for degradation by the proteasome through ubiquitination, reducing their abundance and signaling potential.
* **Phosphorylation and Inactivation:** Specific phosphorylation events on PRR molecules can disrupt their ability to interact with downstream signaling components, effectively switching them off.

2. **Signal Inhibition:** Negative regulators act at various points in the signaling cascade, blocking signal propagation and preventing excessive activation:
* **Inhibitory Kinases:** Kinases like IRAK-M and TBK1 can phosphorylate and inhibit downstream signaling molecules, such as TRAF6 and IRF3, respectively, preventing the formation of signaling complexes.
* **Deubiquitinases:** Enzymes that remove ubiquitin chains from signaling proteins can disrupt the formation of signaling complexes, dampening the signal.
* **Adaptor Protein Inhibition:** Proteins like A20 and CYLD can inhibit the activity of adaptors like TRAF6 and TRADD, which are essential for signaling complex formation and activation.

3. **Feedback Loops:** Negative feedback loops are crucial for maintaining homeostasis and preventing uncontrolled activation. For example, activated transcription factors like NF-κB can induce the expression of negative regulators, ultimately dampening their own activation.

4. **Immune Tolerance:** Negative regulation is critical for maintaining immune tolerance, preventing the activation of immune responses against self-antigens. This is achieved through mechanisms like:
* **Anergy:** Negative regulators can induce a state of anergy in immune cells, preventing them from responding to certain stimuli.
* **Treg Cell Activity:** Regulatory T cells (Tregs) express specific transcription factors and surface receptors that actively suppress immune responses, contributing to the maintenance of immune tolerance.

Overall, negative regulation of cytoplasmic pattern recognition receptor signaling pathway is a dynamic and essential process that fine-tunes the immune response, ensuring appropriate activation while preventing excessive inflammation and maintaining immune tolerance. This intricate interplay of molecular mechanisms is critical for maintaining homeostasis and protecting the organism from both infection and autoimmune disease.'
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Proteins (1)

Compounds (2)