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Physiopathological aspects of the Wnt/β-catenin signaling pathway in the male reproductive system.

Lombardi AP, Royer C, Pisolato R, Cavalcanti FN, Lucas TF, Lazari MF, Porto CS - Spermatogenesis (2013)

Bottom Line: The Wnt/β-catenin signaling pathway controls several biological processes throughout development and adult life.Dysregulation of Wnt/β-catenin signaling underlies a wide range of pathologies in animals and humans, including cancer in different tissues.Our understanding of the role of Wnt/β-Catenin signaling in male reproductive tissues is still evolving, and several questions are open to be addressed in the future.

View Article: PubMed Central - PubMed

Affiliation: Section of Experimental Endocrinology; Department of Pharmacology; Escola Paulista de Medicina; Universidade Federal de São Paulo; São Paulo, SP Brazil.

ABSTRACT
The Wnt/β-catenin signaling pathway controls several biological processes throughout development and adult life. Dysregulation of Wnt/β-catenin signaling underlies a wide range of pathologies in animals and humans, including cancer in different tissues. In this review, we provide an update of the Wnt/β-catenin signaling pathway and the possible roles of the Wnt/β-catenin signaling in the biology of testis, epididymis and prostate. Data from our laboratory suggest the involvement of 17β-estradiol and estrogen receptors (ERs) on the regulation of β-catenin expression in rat Sertoli cells. We also provide emerging evidences of the involvement of Wnt/β-catenin pathway in testis and prostate cancer. Our understanding of the role of Wnt/β-Catenin signaling in male reproductive tissues is still evolving, and several questions are open to be addressed in the future.

No MeSH data available.


Related in: MedlinePlus

Figure 1. A new Wnt/β-catenin signaling model based on the study from Li et al.27 (A) In the absence of Wnt protein (Off State), the destruction complex (Axin, GSK3, CK1, APC and Dvl) resides in the cytoplasm, where it binds, phosphorylates, and ubiquitinates β-catenin by β-TrCP. The proteasome recycles the complex by degrading β-catenin. (B) In the presence of Wnt (On State), this protein induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex stills captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates (Adapted from Clevers and Nusse2).
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Figure 1: Figure 1. A new Wnt/β-catenin signaling model based on the study from Li et al.27 (A) In the absence of Wnt protein (Off State), the destruction complex (Axin, GSK3, CK1, APC and Dvl) resides in the cytoplasm, where it binds, phosphorylates, and ubiquitinates β-catenin by β-TrCP. The proteasome recycles the complex by degrading β-catenin. (B) In the presence of Wnt (On State), this protein induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex stills captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates (Adapted from Clevers and Nusse2).

Mentions: In cells not exposed to Wnt signals (Fig. 1A), phosphorylation and degradation of cytosolic β-catenin is observed by the action of the Axin complex. The scaffolding protein Axin has separate domains that interact with glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and β-catenin, and coordinates sequential phosphorylation of β-catenin at serine 45 by CK1α, and threonine 41, serine 37 and serine 33 by GSK3.24 The phosphorylation of β-catenin at serine 33 and 37 creates a binding site for the β-TrCP, an E3 ubiquitin ligase subunit, which leads to β-catenin ubiquitination and degradation.25 Axin also contains a regulator of G protein signaling domain that interacts with adenomatous polyposis coli tumor suppressor protein (APC). In addition to β-catenin, GSK3 and CK1 phosphorylate Axin and APC, leading to increased association of Axin and APC with β-catenin, and thus enhanced phosphorylation/degradation of β-catenin.24 Degradation of β-catenin prevents β-catenin from reaching the nucleus, and Wnt target genes are thereby repressed by the DNA-bound T cell factor/lymphoid enhancer factor (TCF/LEF) family of proteins. TCF represses gene expression by interacting with the repressor Groucho (TLE1 in human), which promotes histone deacetylation and chromatin compaction (for a review, see refs. 26 and 2).


Physiopathological aspects of the Wnt/β-catenin signaling pathway in the male reproductive system.

Lombardi AP, Royer C, Pisolato R, Cavalcanti FN, Lucas TF, Lazari MF, Porto CS - Spermatogenesis (2013)

Figure 1. A new Wnt/β-catenin signaling model based on the study from Li et al.27 (A) In the absence of Wnt protein (Off State), the destruction complex (Axin, GSK3, CK1, APC and Dvl) resides in the cytoplasm, where it binds, phosphorylates, and ubiquitinates β-catenin by β-TrCP. The proteasome recycles the complex by degrading β-catenin. (B) In the presence of Wnt (On State), this protein induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex stills captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates (Adapted from Clevers and Nusse2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3644045&req=5

Figure 1: Figure 1. A new Wnt/β-catenin signaling model based on the study from Li et al.27 (A) In the absence of Wnt protein (Off State), the destruction complex (Axin, GSK3, CK1, APC and Dvl) resides in the cytoplasm, where it binds, phosphorylates, and ubiquitinates β-catenin by β-TrCP. The proteasome recycles the complex by degrading β-catenin. (B) In the presence of Wnt (On State), this protein induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex stills captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates (Adapted from Clevers and Nusse2).
Mentions: In cells not exposed to Wnt signals (Fig. 1A), phosphorylation and degradation of cytosolic β-catenin is observed by the action of the Axin complex. The scaffolding protein Axin has separate domains that interact with glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), and β-catenin, and coordinates sequential phosphorylation of β-catenin at serine 45 by CK1α, and threonine 41, serine 37 and serine 33 by GSK3.24 The phosphorylation of β-catenin at serine 33 and 37 creates a binding site for the β-TrCP, an E3 ubiquitin ligase subunit, which leads to β-catenin ubiquitination and degradation.25 Axin also contains a regulator of G protein signaling domain that interacts with adenomatous polyposis coli tumor suppressor protein (APC). In addition to β-catenin, GSK3 and CK1 phosphorylate Axin and APC, leading to increased association of Axin and APC with β-catenin, and thus enhanced phosphorylation/degradation of β-catenin.24 Degradation of β-catenin prevents β-catenin from reaching the nucleus, and Wnt target genes are thereby repressed by the DNA-bound T cell factor/lymphoid enhancer factor (TCF/LEF) family of proteins. TCF represses gene expression by interacting with the repressor Groucho (TLE1 in human), which promotes histone deacetylation and chromatin compaction (for a review, see refs. 26 and 2).

Bottom Line: The Wnt/β-catenin signaling pathway controls several biological processes throughout development and adult life.Dysregulation of Wnt/β-catenin signaling underlies a wide range of pathologies in animals and humans, including cancer in different tissues.Our understanding of the role of Wnt/β-Catenin signaling in male reproductive tissues is still evolving, and several questions are open to be addressed in the future.

View Article: PubMed Central - PubMed

Affiliation: Section of Experimental Endocrinology; Department of Pharmacology; Escola Paulista de Medicina; Universidade Federal de São Paulo; São Paulo, SP Brazil.

ABSTRACT
The Wnt/β-catenin signaling pathway controls several biological processes throughout development and adult life. Dysregulation of Wnt/β-catenin signaling underlies a wide range of pathologies in animals and humans, including cancer in different tissues. In this review, we provide an update of the Wnt/β-catenin signaling pathway and the possible roles of the Wnt/β-catenin signaling in the biology of testis, epididymis and prostate. Data from our laboratory suggest the involvement of 17β-estradiol and estrogen receptors (ERs) on the regulation of β-catenin expression in rat Sertoli cells. We also provide emerging evidences of the involvement of Wnt/β-catenin pathway in testis and prostate cancer. Our understanding of the role of Wnt/β-Catenin signaling in male reproductive tissues is still evolving, and several questions are open to be addressed in the future.

No MeSH data available.


Related in: MedlinePlus