CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

Jiyuan Sun

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CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

作者：

Jiyuan Sun

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protein-coupled

receptor

Β-ARRESTIN

CARD

recruited

membrane

associated

protein

Nuclear

factor-κB

Cancer

ATHEROGENESIS

摘要：

CARD recruited membrane associated protein 3 (CARMA3) is a novel scaffold protein. It belongs to the CARMA protein family, and is known to activate nuclear factor (NF)- κB. However, it is still unknown which receptor functions upstream of CARMA3 to trigger NF-κB activation. Recently, several studies have demonstrated that CARMA3 serves as an indispensable adaptor protein in NF-κB signaling under some G protein-coupled receptors (GP- CRs), such as lysophosphatidic acid (LPA) receptor and angiotensin (Ang) Ⅱ receptor. Mechanistically, CARMA3 recruits its essential downstream molecules Bcl10 and MALT1 to form the CBM (CARMA3-Bcl10-MALT1) signalosome whereby it triggers NF-κB activation. GPCRs and NF-κB play pivotal roles in the regulation of various cellular functions, therefore, aberrant regulation of the GPCR/NF-κB signaling axis leads to the development of many types of diseases, such as cancer and atherogenesis. Recently, the GPCR/CARMA3/NF-κB signaling axis has been confirmed in these specific diseases and it plays crucial roles in the pathogenesis of disease progression. In ovarian cancer cell lines, knockdown of CARMA3 abolishes LPA receptor-induced NF-κB activation, and reduces LPA-induced ovarian cancer invasion. In vascular smooth cells, downregulation of CARMA3 substantially impairs Ang-Ⅱ-receptor-induced NF-κB activation, and in vivo studies have confirmed that Bcl10- deficient mice are protected from developing Ang-Ⅱ-receptor-induced atherosclerosis and aortic aneurysms. In this review, we summarize the biology of CARMA3, describe the role of the GPCR/CARMA3/NF-κB signaling axis in ovarian cancer and atherogenesis, and speculate about the potential roles of this signaling axis in other types of cancer and diseases. With a significant increase in the identification of LPA- and Ang-Ⅱ-like ligands, such as endothelin-1, which also activates NF-κB via CARMA3 and contributes to the development of many diseases, CARMA3 is emerging as a novel therapeutic target for various types of cancer a

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篇名	CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases
来源期刊	世界生物化学杂志：英文版（电子版）	学科	医学
关键词	G protein-coupled receptor Β-ARRESTIN CARD recruited membrane associated protein 3 Nuclear factor-κB Cancer ATHEROGENESIS
年，卷（期）	2010,（12）	所属期刊栏目
研究方向		页码范围	353-361
页数	9页	分类号	R363
字数		语种
DOI