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The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria.

Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM - Mediators Inflamm. (2014)

Bottom Line: During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation.The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury.Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections.

View Article: PubMed Central - PubMed

Affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km. 9.5 s/n Carretera Morelia-Zinapécuaro, La Palma, Tarímbaro, 58893 Morelia, MICH, Mexico.

ABSTRACT
Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/β-catenin signaling pathway. We think that a deep insight into the role of Wnt/β-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases.

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Related in: MedlinePlus

The Wnt/β-catenin pathway. In the absence of stimulus (Wnt off), β-catenin is constantly phosphorylated by CKIα and GSK3β. These phosphorylations constitute a signal for β-catenin polyubiquitination and hydrolysis by the proteasome 26S. In the presence of Wnt protein ligands (Wnt on), the destruction complex constituted by the proteins APC, Axin, CKIα, and GSK3 is inactivated and β-catenin, which is constantly synthetized, accumulates in the cytoplasm and nucleus where it interacts with TCF/LEF transcription factors to enhance expression of specific genes.
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Related In: Results  -  Collection


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fig1: The Wnt/β-catenin pathway. In the absence of stimulus (Wnt off), β-catenin is constantly phosphorylated by CKIα and GSK3β. These phosphorylations constitute a signal for β-catenin polyubiquitination and hydrolysis by the proteasome 26S. In the presence of Wnt protein ligands (Wnt on), the destruction complex constituted by the proteins APC, Axin, CKIα, and GSK3 is inactivated and β-catenin, which is constantly synthetized, accumulates in the cytoplasm and nucleus where it interacts with TCF/LEF transcription factors to enhance expression of specific genes.

Mentions: β-Catenin is not detectable in the cytoplasm or nucleus in unstimulated cells because free β-catenin levels (the form not bound to the E-cadherin complex) is controlled by the destruction complex. This complex is composed mainly by the tumor suppressor adenomatous polyposis coli (APC) and Axin, which function as scaffolding proteins on which the Ser/Thr kinases casein kinase 1α (CK1α) and glycogen synthase kinase 3β (GSK3β) phosphorylate β-catenin at the N-terminal residues Ser45, Ser33, Ser37, and Thr41 [3]. These phosphorylations label β-catenin to be polyubiquitinated by the Skp1-Cdc53-F-Box E3 ubiquitin ligase complex (SCFβ-TRCP) and degraded by the proteasome 26S (Figure 1, Wnt Off). GSK3α is also able to regulate β-catenin phosphorylation in vitro and in vivo, which indicates that both isoforms of GSK3 contribute to maintain low levels of β-catenin in basal conditions [4].


The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria.

Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM - Mediators Inflamm. (2014)

The Wnt/β-catenin pathway. In the absence of stimulus (Wnt off), β-catenin is constantly phosphorylated by CKIα and GSK3β. These phosphorylations constitute a signal for β-catenin polyubiquitination and hydrolysis by the proteasome 26S. In the presence of Wnt protein ligands (Wnt on), the destruction complex constituted by the proteins APC, Axin, CKIα, and GSK3 is inactivated and β-catenin, which is constantly synthetized, accumulates in the cytoplasm and nucleus where it interacts with TCF/LEF transcription factors to enhance expression of specific genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127235&req=5

fig1: The Wnt/β-catenin pathway. In the absence of stimulus (Wnt off), β-catenin is constantly phosphorylated by CKIα and GSK3β. These phosphorylations constitute a signal for β-catenin polyubiquitination and hydrolysis by the proteasome 26S. In the presence of Wnt protein ligands (Wnt on), the destruction complex constituted by the proteins APC, Axin, CKIα, and GSK3 is inactivated and β-catenin, which is constantly synthetized, accumulates in the cytoplasm and nucleus where it interacts with TCF/LEF transcription factors to enhance expression of specific genes.
Mentions: β-Catenin is not detectable in the cytoplasm or nucleus in unstimulated cells because free β-catenin levels (the form not bound to the E-cadherin complex) is controlled by the destruction complex. This complex is composed mainly by the tumor suppressor adenomatous polyposis coli (APC) and Axin, which function as scaffolding proteins on which the Ser/Thr kinases casein kinase 1α (CK1α) and glycogen synthase kinase 3β (GSK3β) phosphorylate β-catenin at the N-terminal residues Ser45, Ser33, Ser37, and Thr41 [3]. These phosphorylations label β-catenin to be polyubiquitinated by the Skp1-Cdc53-F-Box E3 ubiquitin ligase complex (SCFβ-TRCP) and degraded by the proteasome 26S (Figure 1, Wnt Off). GSK3α is also able to regulate β-catenin phosphorylation in vitro and in vivo, which indicates that both isoforms of GSK3 contribute to maintain low levels of β-catenin in basal conditions [4].

Bottom Line: During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation.The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury.Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections.

View Article: PubMed Central - PubMed

Affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km. 9.5 s/n Carretera Morelia-Zinapécuaro, La Palma, Tarímbaro, 58893 Morelia, MICH, Mexico.

ABSTRACT
Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/β-catenin signaling pathway. We think that a deep insight into the role of Wnt/β-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases.

Show MeSH
Related in: MedlinePlus