Mammalian sterile 20-like kinase 1/2 inhibits the Wnt/β-catenin signalling pathway by directly binding casein kinase 1ε

Xu, Fei; Wang, Yanlin; Chang, Jiao-Jiao; Du, Sichen; Diao, Lei; Jiang, Nan; Wang, Huijun; Ma, Ding; Zhang, Jin

doi:10.1042/bj20130986

Cited by 20 publications

(26 citation statements)

References 44 publications

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“…Xu and co-workers recently postulated the interaction of the Hippo and Wnt pathway via CK1ε. Herein, the Hippo upstream kinase MST1 is able to suppress the Wnt/β-catenin pathway by directly binding CK1ε, thereby preventing phosphorylation of DVL (Figure 8B) (332). …”

Section: Participation Of Ck1 In the Development Of Cancermentioning

confidence: 99%

The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis

et al. 2014

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Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key proteins in signal transduction and signal integration molecules. In line with this notion, CK1 is tightly connected to the regulation and degradation of β-catenin, p53, and MDM2. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions, it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, scientific effort has enormously increased (i) to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii) to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review, we summarize the current knowledge regarding CK1 regulation, function, and interaction with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

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Section: Participation Of Ck1 In the Development Of Cancermentioning

confidence: 99%

The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis

et al. 2014

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“…Seeing that Mst1/2 and Lats1/2 can phosphorylate Taz, they are thought to be able to repress Wnt as well (Kim and Jho, 2014). In summary, the Hippo pathway can repress Wnt signaling by blocking Dvl or maintaining β-catenin in the cytoplasm, however, the contribution of the interaction between the Hippo and Wnt pathways to organ size regulation remains unknown (Xu et al, 2014). …”

Section: Interplay With Other Signaling Pathwaysmentioning

confidence: 99%

Hippo Pathway and Skeletal Muscle Mass Regulation in Mammals: A Controversial Relationship

2017

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Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. In addition, satellite cell inclusion may contribute to increase muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a few studies looked at the involvement of the newly discovered Hippo pathway in the regulation of muscle mass. In line with its roles in other organs, it has been hypothesized that the Hippo pathway could play a role in different regulatory mechanisms in skeletal muscle as well, namely proliferation and renewal of satellite cells, differentiation, death, and growth of myogenic cells. While the Hippo components have been identified in skeletal muscle, their role in muscle mass regulation has been less investigated and conflicting results have been reported. Indeed, the first studies described both atrophic and hypertrophic roles of the Hippo pathway and its effectors Yap/Taz using different biochemical approaches. Further, investigation is therefore warranted to determine the role of the Hippo pathway in the regulation of skeletal muscle mass. New components of the pathway will probably emerge and unsuspected roles will likely be discovered due to its numerous interactions with different cellular processes. This mini-review aims to summarize the current literature concerning the roles of the Hippo pathway in the regulation of muscle mass and to develop the hypothesis that this pathway could contribute to muscle mass adaptation after exercise.

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“…Co-IP and GST Pull-down Assays-Co-IP and GST pulldown assays were conducted as described previously (35). For the GST pull-down assay, 293T cells were cotransfected with the plasmids expressing the GST-His 8 -tagged TRB3 and AMPK␣.…”

Section: Methodsmentioning

confidence: 99%

Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice

Li¹,

Xiao²,

et al. 2016

Journal of Biological Chemistry

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Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously. The aim of our current study is to investigate the role of ATF4 in alcoholic liver steatosis and elucidate the underlying mechanisms. Here, we showed that the expression of ATF4 is induced by ethanol in hepatocytes in vitro and in vivo, and liverspecific ATF4 knock-out mice are resistant to ethanol-induced liver steatosis, associated with stimulated hepatic AMP-activated protein kinase (AMPK) activity. Furthermore, adenovirus-mediated AMPK knockdown significantly reversed the suppressive effects of ATF4 deficiency on ethanol-induced liver steatosis in mice. In addition, ethanol-fed ATF4 knock-out mice exhibit AMPK-dependent inhibition of fatty acid synthase and stimulation of carnitine palmitoyltransferase 1 (CPT1) in the liver. Moreover, hepatic Tribbles homolog 3 (TRB3) expression was stimulated by ethanol in an ATF4-dependent manner, and adenovirus-mediated TRB3 knockdown blocked ATF4-dependent ethanol-induced AMPK inhibition and triglyceride accumulation in AML-12 cells. Finally, TRB3 directly interacted with AMPK to suppress its phosphorylation. Taken together, these results identify the ATF4-TRB3-AMPK axis as a novel pathway responsible for ethanol-induced liver steatosis.People consuming excessive amounts of alcohol for prolonged periods suffer from alcoholic liver disease, which encompasses fatty liver, hepatic inflammation and necrosis, progressive fibrosis, and hepatocellular carcinoma (1). Alcoholic fatty liver is the early stage of alcoholic liver disease, characterized by increased accumulation of fat in the liver, which is usually caused by increased free fatty acid (FFA) 4 uptake, augmented de novo lipogenesis, decreased ␤-oxidation, and/or impaired triglyceride (TG) export (2). Studies have identified some important regulators for ethanol-induced liver steatosis, including sirtuin 1 (SIRT1) (3), sterol regulatory element-binding protein 1 (SREBP-1) (4), peroxisome proliferator-activated receptor ␥ coactivator 1-␣ (PGC-1␣) (5), and 5Ј-adenosine monophosphate-activated protein kinase (AMPK) (6 -8).Among them, AMPK is one of the most important regulators (6 -8). AMPK is a heterotrimeric complex consisting of a catalytic ␣ subunit and two regulatory ␤/␥ subunits. It acts as a key metabolic "switch" by phosphorylating target enzymes involved in lipid metabolism, such as acetyl-CoA carboxylase (ACC) (9). Malonyl-CoA, the product of ACC, is both a precursor for fatty acid biosynthesis and a potent inhibitor of ␤-oxidation at the step regulated by carnitine palmitoyltransferase I (10). AMPK activity is suppressed under ethanol exposure (6) and activation of AMPK by its activator (5-aminoimidazole-4-carboxamide 1-␤-D-ribofuranoside) or metformin prevents ethanol-induced liver steatosis (11, 12). However, the molecular mechanisms underlying ethanol suppression of AMPK activity remain largely unknown. Activating...

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Mammalian sterile 20-like kinase 1/2 inhibits the Wnt/β-catenin signalling pathway by directly binding casein kinase 1ε

Cited by 20 publications

References 44 publications

The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis

The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis

Hippo Pathway and Skeletal Muscle Mass Regulation in Mammals: A Controversial Relationship

Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice

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