NLRC3

Official Full Name

NLR family CARD domain containing 3

Organism

Homo sapiens

Gene ID

197358

Background

This gene encodes a NOD-like receptor family member. The encoded protein is a cytosolic regulator of innate immunity. This protein directly interacts with stimulator of interferon genes (STING), to prevent its proper trafficking, resulting in disruption of STING-dependent activation of the innate immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Synonyms

NOD3; CLR16.2

Cat.No.	Product Name	Price
CSC-DC010429	Panoply™ Human NLRC3 Knockdown Stable Cell Line	Inquiry
CSC-SC010429	Panoply™ Human NLRC3 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10830Z	Human NLRC3 adenoviral particles	Inquiry
LV19621L	human NLRC3 (NM_178844) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH352860	shRNA set against Human NLRC3 (NM_178844.2)	Inquiry
SHH352865	shRNA set against Mouse NLRC3 (NM_001081280.1)	Inquiry
SHR012676	shRNA set against Human NLRC3(NM_178844.2)	Inquiry
SHR012694	shRNA set against Mouse Nlrc3(NM_001081280.1)	Inquiry

Cat.No.	Product Name	Price
MiUTR1H-06792	NLRC3 miRNA 3'UTR clone	Inquiry
MiUTR1M-07683	NLRC3 miRNA 3'UTR clone	Inquiry
CDCB189441	Rabbit NLRC3 ORF clone (XM_008250669.1)	Inquiry
CDCL138643	Human NLRC3 ORF clone (NM_178844.2)	Inquiry
CDCL138645	Human Nlrc3 ORF clone (NM_001081280.1)	Inquiry

Detailed Information

NLRC3 is a NOD-like receptor family 3 with a CARD (caspase-recruitment domain) domain. It is a newly discovered non-inflammatory corpuscle family member that is highly expressed in immune cells and is an evolutionarily highly conserved intracytoplasmic pattern recognition receptor encoded by the chromosome 16 gene. The study found that NLRC3 has the function of inflammation and tumor signaling through checkpoints, which can negatively regulate NF-κB activation and IFN-I production to attenuate inflammation and immune response, and also inhibit cell proliferation by inhibiting the activation of PI3KmTOR signaling axis. Anti-tumor function, therefore, when its expression is abnormal and do not normally exercise the regulatory function, it can cause abnormal pathophysiological reactions that cause damage to the body, trigger abnormal diseases, autoimmune diseases and tumors, and affect the occurrence, development and outcome of the disease.

NLRC3 Features

The study found that NLRC3 is highly expressed in immune cells, especially T lymphocytes, and prevents IκBα (inhibitor of NF-κB, alpha) degradation by inhibiting the activation of the inhibitory nuclear factor kappa-B kinase (IkB kinase). The heterodimer p50:p65 and IκBα dissociation and activation of NF-κB were blocked, and p50:p65 could not enter the nucleus to initiate transcription of specific genes, and as a result, T cell activation was inhibited.

Gültekin et al. found that NLRC3 also negatively regulates inflammatory responses by interacting with subunits of inflammatory corpuscle complexes. NLRC3 competes with NLRP3/cryopyrin for apoptosis-associated spot-like protein (ASC) in a CARD-CARD manner and bridges pro-caspase-1 and pro-caspase5 to form an inflammatory small body-like complex. When NLRC3 binds to ASC, it inhibits and maintains ASC in a non-activated state, leading to pro-caspase cleavage and pro-IL-1β maturation and secretion disorders, which inhibits NLR-mediated inflammation.

Nlrc3 Figure 1. NLRC3-regulated inflammation pathways. (Sharma, N., et al. 2017)

NLRC3 and Tumor

NLRC3 not only has anti-inflammatory and immunosuppressive effects, but is also closely related to tumors. Rajendra Karki et al. found that decreased expression of NLRC3 promoted tumorigenesis, while high expression of NLRC3 inhibited tumor development, confirming that NLRC3 is a negative regulator of the PI3K-AKT-mTOR pathway. By inhibiting the activation of this pathway, NLRC3 can inhibit inflammatory responses, regulate cell proliferation, and inhibit tumorigenesis. In the clinical study of hepatocellular carcinoma, the overall 5-year cumulative survival rate was 60.7% and 32.8% in NLRC3 high-expression and low-expression patients, respectively, indicating poor prognosis in patients with low NLRC3 expression. In addition, with the increase of tumor stage, the expression of NLRC3 is getting lower and lower, and its expression level is the lowest in stage IV tumor tissues.

NLR family members NLRC3 molecules are cytoplasmic pattern recognition receptors that negatively regulate inflammatory cell activation and inflammatory cytokine production in inflammation and immune responses. In the Nlrc3-/- mouse enteritis-associated intestinal tumor model, inflammatory cells such as neutrophils, macrophages, and NK in local colon tissue of Nlrc3-/- mice were compared with WT mice. Cells and inflammatory cytokines (IL-1β, IL-6, TNF G-CSF, CXCL1, CCL2, CCL3, etc.) were significantly elevated. At the same time, the levels of IL-6, G-CSF, CXCL1, CCL3 and other factors in the circulatory system also increased significantly. Immunoblotting also revealed increased levels of phosphorylation of IκBα and STAT3. Further results showed that the inflammation, ulceration, hyperplasia and damage of colon tissue of Nlrc3-/- mice were more severe than those of WT mice. Finally, intestinal epithelial cells of Nlrc3-/- mice undergo malignant transformation and form a large number of highly differentiated intestinal malignant tumors. This result indicates that the NLRC3-deficient organism loses its inflammatory pathways during inflammation and immune response.

References:

Sharma, N. , & Jha, S. . (2017). Nlrc3 mediated pi3k-mtor inhibition takes a toll on colon cancer. Translational Cancer Research, 6(S2), S296-S300.
Liu, R. , Truax, A. D. , Chen, L. , Hu, P. , Li, Z. , & Chen, J. , et al. (2015). Expression profile of innate immune receptors, nlrs and aim2, in human colorectal cancer: correlation with cancer stages and inflammasome components. Oncotarget, 6(32).
Karki, R. , Man, S. M. , Malireddi, R. K. S. , Kesavardhana, S. , Zhu, Q. , & Burton, A. R. , et al. (2016). Nlrc3 is an inhibitory sensor of pi3k–mtor pathways in cancer. Nature, 540(7634), 583-587.

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