Proteolytic cleavage of β‐catenin by caspases: an in vitro analysis

Craen, Marc Van de; Berx, Geert; Brande, Ilse van den; Fiers, Walter; Declercq, Wim; Vandenabeele, Peter

doi:10.1016/s0014-5793(99)01153-9

Cited by 45 publications

(33 citation statements)

References 44 publications

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“…To address this supposition directly, we sought to identify the substrate by which caspase 3 or 8 may limit canonical signaling activity. Interestingly, ␤-catenin, the central component of the canonical Wnt pathway, is a known substrate of effector caspases (3, 6, 7) during apoptosis (62,66). Accordingly, we noted that ␤-catenin immunoblot FIG.…”

Section: Fig 3 Limited Canonical Wnt/␤-catenin Signaling In the Myomentioning

confidence: 70%

“…There is evidence suggesting that noncanonical Wnt signaling actively inhibits the canonical Wnt/␤-catenin pathway by enhancing ␤-catenin degradation through an as-yet-undefined mechanism (46,64). Interestingly, caspase proteases have been shown to target and cleave ␤-catenin, leading to a loss of canonical Wnt signal activity (62,66). Caspase activity is typically associated with apoptosis/programmed cell death, yet a growing body of evidence suggests that this protease family mediates cell fate decisions that are distinct from apoptosis/cell death (1,15).…”

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confidence: 99%

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Wnt11 Promotes Cardiomyocyte Development by Caspase-Mediated Suppression of Canonical Wnt Signals

Abdul‐Ghani

Dufort

Stiles

et al. 2011

Molecular and Cellular Biology

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Specification and early patterning of the vertebrate heart are dependent on both canonical and noncanonical wingless (Wnt) signal pathways. However, the impact of each Wnt pathway on the later stages of myocardial development and differentiation remains controversial. Here, we report that the components of each Wnt signal conduit are expressed in the developing and postnatal heart, yet canonical/␤-catenin activity is restricted to nonmyocardial regions. Subsequently, we observed that noncanonical Wnt (Wnt11) enhanced myocyte differentiation while preventing stabilization of the ␤-catenin protein, suggesting active repression of canonical Wnt signals. Wnt11 stimulation was synonymous with activation of a caspase 3 signal cascade, while inhibition of caspase activity led to accumulation of ␤-catenin and a dramatic reduction in myocyte differentiation. Taken together, these results suggest that noncanonical Wnt signals promote myocyte maturation through caspasemediated inhibition of ␤-catenin activity.

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Section: Fig 3 Limited Canonical Wnt/␤-catenin Signaling In the Myomentioning

confidence: 70%

mentioning

confidence: 99%

Wnt11 Promotes Cardiomyocyte Development by Caspase-Mediated Suppression of Canonical Wnt Signals

Abdul‐Ghani

Dufort

Stiles

et al. 2011

Molecular and Cellular Biology

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“…In atretic follicles of porcine ovaries, β-catenin expr ession is re duced concomitan tly with decreased cadherin expression. Cleaved β-catenin was detected in early atretic follicles, and the cleavage of β-catenin is probably mediated by caspases, which are essential factors of intracellular signal transduction of apoptosis [37][38][39]. Therefore, it is assumed that apoptotic signals, such as binding of Fas-ligand and tumor necrosis factors etc.…”

Section: Discussionmentioning

confidence: 99%

Changes in Cell Adhesion Molecules during Follicular Atresia in Porcine Ovaries.

Nishihara

Manabe

Nakayama

et al. 2000

Journal of Reproduction and Development

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Abstract. Determination of the expression level and localization of cell adhesion molecules is crucial for understanding the mechanism of maintenance and remodeling of the ovarian follicle structure. We immunocytochemically investigated expression of the cell adhesion molecules, "classic" cadherins and β-catenin, in developing and/or atretic follicles of porcine ovaries. Healthy follicles showed strong staining for cadherin-8 and β-catenin in granulosa cells tightly attached to the basement membrane, and moderate/weak staining was seen on the inner surface of the granulosa cell layer. Strong VE-cadherin expression was seen in a single cell layer attached to the basement membrane in the theca interna layer of healthy follicles. The expression of cadherin-8, β-catenin and VE-cadherin decreased during follicular atresia. No positive staining was observed for R-cadherin, E-cadherin, Tcadherin, BR-cadherin or P-cadherin, and a weak positive reaction for N-cadherin was seen only in the granulosa cells of healthy and early atretic follicles. These findings indicate that cadherin-8, Ncadherin and VE-cadherin have important roles in follicular development and/or degeneration, and that decreases in the expression of these cadherins are involved in follicular atresia in porcine follicles.

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“…Previous reports have demonstrated that b-catenin is cleaved by caspases 3, 6, and 8 (23,24). To investigate whether one or more of these caspases were responsible for the truncated b-catenin proteins, we first used STS to induce caspase activity in the wild-type cells and compared their b-catenin products with those found in the untreated, nonadherent Tsc2 2/2 cells and with STS-treated, adherent Tsc2 2/2 cells.…”

Section: Caspase 3 Activity Contributes To B-catenin Cleavagementioning

confidence: 99%

The Loss of Tuberin Promotes Cell Invasion through the β-Catenin Pathway

Barnes

Kenerson

Mak

et al. 2010

Am J Respir Cell Mol Biol

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Mutations in the tumor suppressor tuberin (TSC2) are a common factor in the development of lymphangioleiomyomatosis (LAM). LAM is a cystic lung disease that is characterized by the infiltration of smooth muscle-like cells into the pulmonary parenchyma. The mechanism by which the loss of tuberin promotes the development of LAM has yet to be elucidated, although several lines of evidence suggest it is due to the metastasis of tuberin-deficient cells. Here we show that tuberin-null cells become nonadherent and invasive. These nonadherent cells express cleaved forms of b-catenin. In reporter assays, the b-catenin products are transcriptionally active and promote MMP7 expression. Invasion by the tuberin-null cells is mediated by MMP7. Examination of LAM tissues shows the expression of cleaved b-catenin products and MMP7 consistent with a model that tuberin-deficient cells acquire invasive properties through a b-catenin-dependent mechanism, which may underlie the development of LAM.Keywords: caspase 3; MMP7; LAM; tuberous sclerosis complex Lymphangioleiomyomatosis (LAM) is a potentially fatal cystic lung disease that occurs almost exclusively in women. There are no proven medical therapies for the treatment of LAM, and the health of patients with LAM deteriorates over an average span of 10 years due to the progressive destruction of the lungs (1). LAM is predominantly caused by tuberin loss-of-function mutations, forming a genetic link with tuberous sclerosis complex (TSC) (2-4). Recent analyses estimate that 30 to 40% of women with TSC may also be affected with LAM (5).TSC is a multisystem disease that results in the growth of benign tumors in the brain, kidneys, heart, and skin. It commonly affects the central nervous system, resulting in any combination of disorders including seizures, mental retardation, and behavioral problems (6). One of the most common phenotypic factors for TSC is the development of renal angiomyolipomas (AMLs), which occur in approximately 70 to 80% of patients with TSC (7,8). AMLs are characterized by the abnormal proliferation of dysplastic vessels and adipose and smooth muscle-like cells. Up to 60% of patients with sporadic LAM are diagnosed with AMLs (9). Genetic analyses have demonstrated that LAM cells and AML cells isolated from patients with LAM contain identical TSC2 mutations, suggesting that tuberin-deficient AML smooth muscle-like cells may have the potential to migrate and infiltrate the lung (3).The benign metastasis hypothesis of LAM is further supported by two independent clinical observations. First, after lung transplantation, there have been several case reports in which LAM develops anew in the transplanted donor lung, with LAM cells expressing the same TSC2 mutation identified in the native lung (10-13). Second, LAM cells have recently been isolated from the circulatory system and other bodily fluids of patients with LAM, indicating that these migratory cells have the potential to invade a variety of host tissues (14). These lines of evidence strongly suggest that the dev...

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Proteolytic cleavage of β‐catenin by caspases: an in vitro analysis

Cited by 45 publications

References 44 publications

Wnt11 Promotes Cardiomyocyte Development by Caspase-Mediated Suppression of Canonical Wnt Signals

Wnt11 Promotes Cardiomyocyte Development by Caspase-Mediated Suppression of Canonical Wnt Signals

Changes in Cell Adhesion Molecules during Follicular Atresia in Porcine Ovaries.

The Loss of Tuberin Promotes Cell Invasion through the β-Catenin Pathway

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