How to Identify PARP14

16 Dec 2025 by AntBio

I. Basic Overview of PARP14

Poly(ADP-ribose) polymerase 14 (PARP14), also known as PARP-4, is a key member of the PARP family, which plays critical roles in DNA repair, immune responses, transcriptional regulation, and cell death. Compared to well-studied members like PARP1 and PARP2, PARP14 has received less attention, but emerging research highlights its involvement in gene expression regulation and its association with various diseases, particularly in immunity, cancer, and inflammation.

Like other PARPs, PARP14 functions through its catalytic activity, transferring ADP-ribose monomers from NAD+ to target proteins, thereby modulating their activity. Unlike PARP1, which primarily acts in DNA damage repair, PARP14 uniquely regulates immune responses, inflammation, and gene expression, integrating multiple signaling pathways to influence cellular physiology.

II. Structure and Catalytic Mechanism of PARP14

PARP14 features a core ADP-ribosyltransferase catalytic domain, enabling it to form poly(ADP-ribose) (PAR) chains on target proteins. This post-translational modification rapidly responds to cellular stimuli, altering signal transduction.

PARP14 also contains specialized domains, such as the WHTH (winged-helix-turn-helix) and BRCT (BRCA1 C-terminal) domains, which mediate protein-protein interactions. The WHTH domain, though capable of DNA binding, is less implicated in DNA repair, while the BRCT domain links PARP14 to DNA repair and protein degradation pathways.Notably, PARP14 modulates transcription factors like NF-κB and AP-1 via ADP-ribosylation, impacting their stability and activity. This regulation fine-tunes cellular responses to external stimuli, particularly in inflammation and immune activation.

III. Role of PARP14 in Immune Regulation

PARP14 and the NF-κB Pathway
NF-κB is a pivotal transcription factor in immunity and inflammation. PARP14 ADP-ribosylates NF-κB subunits (e.g., RelA/p65), enhancing their transcriptional activity and amplifying immune cell responses to pathogens.

Modulation of Immune Cell Function
PARP14 regulates the activity, proliferation, and differentiation of T cells, B cells, and macrophages. For instance, it balances TH1/TH2 cell polarization, shaping adaptive immunity, and influences macrophage cytokine production and phagocytosis.

Immune Tolerance
PARP14 helps maintain immune tolerance by suppressing aberrant immune activation. Dysregulation of PARP14 is linked to autoimmune diseases, where loss of tolerance triggers self-tissue attack.

IV. PARP14 in Cancer

Immune Evasion
PARP14 promotes an immunosuppressive tumor microenvironment, aiding cancer cells in evading immune surveillance. Its overexpression correlates with impaired antitumor immunity.

Cancer Immunotherapy
As a potential target for immunotherapy, PARP14 inhibition may enhance immune checkpoint blockade efficacy by reversing immune suppression.

Tumor Cell Proliferation
PARP14 drives cancer progression by regulating cell-cycle proteins. Elevated PARP14 expression associates with aggressive, metastatic cancers, suggesting therapeutic targeting opportunities.

V. PARP14 in Inflammatory Responses

Acute Inflammation
PARP14 amplifies NF-κB-mediated cytokine production during infections, bolstering host defense.

Chronic Inflammation
Sustained PARP14 activity contributes to chronic inflammatory diseases (e.g., diabetes, cardiovascular disorders). Inhibiting PARP14 may mitigate inflammation-driven pathology.

VI. Clinical Potential of PARP14

PARP14 inhibitors hold promise for cancer (by restoring immune function), autoimmune diseases, and chronic inflammation. Challenges include developing selective inhibitors and defining optimal therapeutic windows.

Conclusion

PARP14 is a multifunctional regulator of immunity, inflammation, and cancer. Its roles in immune evasion and chronic disease underscore its therapeutic potential. Future research should clarify mechanistic details and advance PARP14-targeted therapies.

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