Biosynthesis of dystroglycan: processing of a precursor propeptide

Holt, Kathleen H.; Crosbie, Rachelle H.; Venzke, David; Campbell, Kevin P.

doi:10.1016/s0014-5793(00)01195-9

Cited by 162 publications

(131 citation statements)

References 36 publications

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“…Since DG subunits are encoded by a single gene and are formed upon cleavage of a precursor protein (Henry and Campbell, 1999;Holt et al, 2000;Esapa et al, 2003), detection of the b-DG subunit in the cell lines and in most of the cancers in which a-DG was not detectable (Figs. 1 and 2) suggests that, as previously reported in other types of human malignancies, this lack of detection is likely not due to loss of gene expression but to a specific posttranscriptional mechanism affecting a-DG processing in prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells

Sgambato

Paola

Migaldi

et al. 2007

Journal Cellular Physiology

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Prostate cancer, the most frequently diagnosed cancer in Western men, can display a high variability in term of clinical aggressiveness and prognosis and none of the available markers is able to accurately predict its clinical course. Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two subunits, a-and b-DG, which bind to extracellular matrix molecules and cytoskeleton, respectively. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. This study investigated the role of DG in human prostate tumorigenesis and its suitability as a prognostic marker. The expression level of extracellular a-DG subunit was frequently reduced in human prostate cancer cell lines and primary tumors and the percentage of positive tumor cells was significantly further decreased in vivo following androgen ablation therapy (median ¼ 1%) compared to pre-treatment samples (median ¼ 28%). A significant relationship was observed between a-DG staining on the post-treatment samples and tumor recurrence. A dose-and timedependent decrease of DG expression also occurred in human prostate cancer cells following treatment with the anti-androgen flutamide. Stable expression of an exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a marked inhibition of both anchorage-dependent and independent growth and of the in vivo tumorigenicity. These findings confirm and extend previous evidence that disturbances in the function of the DG complex might contribute to the definition of the malignant behavior of prostate cancer cells and suggest that androgens might regulate DG expression in these cells.

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Section: Discussionmentioning

confidence: 99%

Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells

Sgambato

Paola

Migaldi

et al. 2007

Journal Cellular Physiology

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“…37 It is of interest that overexpression of an exogenous DG cDNA was previously reported to be not able to restore α-DG expression in a series of breast cancer cell lines. 7 We hypothesize that, since DG subunits are encoded by a single gene and are formed upon cleavage of a precursor protein, 6,8 breast cancer cells have developed a specific post-transcriptional mechanism responsible for the lack of expression of α-DG. Overexpression of an exogenous α-DG, however, was previously reported in the T4-2 breast cancer cell line.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 DG is encoded by a single gene and is formed upon cleavage of a precursor protein into two mature subunits which form a tight non-covalent complex. 6,8 The highly and heterogeneously glycosylated cell surface-associated α-DG binds extracellular matrix molecules, such as laminins and agrin. The transmembrane β-DG anchors α-DG to the cell membrane and is linked to the actin cytoskeleton via dystrophin or its paralogue utrophin.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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Dystroglycan (DG) is an adhesion molecule formed by two subunits, α (extracellular) and β (transmembrane) DG, which are codified by a single gene and form a continuous link from the extracellular matrix to the intracellular cytoskeleton. Reduction or loss of expression of DG has been observed in human cancer cell lines and primary tumors and has been suggested to promote tumor development and invasiveness.In this study, the human breast epithelial non-tumorigenic MCF10F and the breast cancer MCF7 cell lines were engineered to stably express an exogenous DG cDNA and the effects on the phenotype of both cell lines were evaluated. The MCF10F transfected cells displayed an increased expression of both DG subunits which was associated with inhibition of the anchorage-dependent growth, accumulation of cells in the G 0 /G 1 phase of the cell cycle and increased adhesion to a substratum. The MCF7 transfected cells were unable to restore α-DG despite an increased expression of the β-DG subunit. Anchoragedependent and independent growth and the in vivo tumorigenicity were reduced in these derivatives that also displayed a reduced adhesion to a substratum and were shown to release α-DG in the culture medium.These findings confirm and extend previous evidence that transformation of mammary epithelial cells is associated with loss of their ability to retain α-DG on the cell membrane. Moreover, they indicate that DG is involved in cell functions other than cell adhesion to the extracellular matrix, and that its loss of function might predispose to tumor progression by compromising regulatory controls over cell growth and proliferation.

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“…The dystroglycan gene (DAG1) encodes a single propeptide which is cleaved to yield two glycoproteins, α-dystroglycan and β-dystroglycan (Holt et al, 2000). The roles of this cleavage and the protease or proteases involved are still unknown.…”

Section: Structure and Biochemistrymentioning

confidence: 99%

Review: Dystroglycan in the Nervous System

Samwald

2007

Nature Precedings

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Dystroglycan is part of a large complex of proteins, the dystrophin-glycoprotein complex, which has been implicated in the pathogenesis of muscular dystrophies for a long time. Besides muscular degeneration many patients manifest symptoms of neurological and cognitive dysfunction. Recent findings suggest that dystroglycan is implicated in brain development, synapse formation and plasticity, nerve-glia interactions and maintenance of the blood-brain barrier. Most research so far has focused on the functions of dystroglycan in muscle and neuromuscular junctions, while its role in the brain and interneuronal synapses has been neglected. This review will give an overview of the biochemistry of dystroglycan, its interaction with other proteins as well as its confirmed and hypothetical functions in the nervous system.

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Biosynthesis of dystroglycan: processing of a precursor propeptide

Cited by 162 publications

References 36 publications

Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells

Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Review: Dystroglycan in the Nervous System

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