Cross-regulation of β-catenin–LEF/TCF and retinoid signaling pathways
نویسندگان
چکیده
Vitamin A derivatives (retinoids) are potent regulators of embryogenesis, cell proliferation, epithelial cell differentiation and carcinogenesis [1]. In breast cancer cells, the effects of retinoids are associated with changes in the cadherin–β-catenin adhesion and signaling system [2,3]. β-catenin is a component of the Wnt signaling pathway, which regulates several developmental pathways [4]. Increases in cytoplasmic β-catenin and β-catenin signaling are also associated with numerous cancers, and are particularly important in colon cancer [5]. The oncogenic and developmental effects of β-catenin are mediated by its interaction with and activation of members of the LEF/TCF family of transcription factors [6–8]. Here, we show that retinoic acid (RA) decreases the activity of the β-catenin–LEF/TCF signaling pathway. This activity of RA was independent of the adenomatous polyposis coli (APC) tumor suppressor and ubiquitination-dependent degradation of cytoplasmic β-catenin. Consistent with this finding, β-catenin interacted directly with the RA receptor (RAR) in a retinoid-dependent manner, but not with the retinoid X receptor (RXR), and RAR competed with TCF for β-catenin binding. The activity of RA on RAR-responsive promoters was also potentiated by β-catenin. The data suggest that direct regulation of β-catenin–LEF/TCF signaling is one mechanism whereby RA influences development, cell differentiation and cancer.
منابع مشابه
The Canonical Wnt Signaling (Wnt/β-Catenin Pathway): A Potential Target for Cancer Prevention and Therapy
Precise regulation of signal transduction pathways is crucial for normal animal development and for maintaining cellular and tissue homeostasis in adults. The Wnt/Frizzled-mediated signaling includes canonical and non-canonical signal transduction pathways. Upregulation or downregulation of the canonical Wnt-signaling (or the Wnt/β-Catenin signal transduction) leads to a variety of human diseas...
متن کاملThe Wnt/β-Catenin Pathway Regulates the Expression of the miR-302 Cluster in Mouse ESCs and P19 Cells
MicroRNAs of the miR-302 cluster are involved in early embryonic development and somatic cell reprogramming. Expression of the miR-302 gene is regulated by the binding of the pluripotency factors Oct4, Sox2 and Nanog to the miR-302 promoter. The specific expression pattern of the miR-302 gene suggested that additional transcription factors might be involved in its regulation. Here, we show that...
متن کاملThe Notch-2 Gene Is Regulated by Wnt Signaling in Cultured Colorectal Cancer Cells
BACKGROUND Notch and Wnt pathways are key regulators of intestinal homeostasis and alterations in these pathways may lead to the development of colorectal cancer (CRC). In CRC the Apc/β-catenin genes in the Wnt signaling pathway are frequently mutated and active Notch signaling contributes to tumorigenesis by keeping the epithelial cells in a proliferative state. These pathways are simultaneous...
متن کاملRole of GAC63 in transcriptional activation mediated by β-catenin
Beta-catenin is a key mediator in the canonical Wnt signaling pathway, which plays important roles in multiple developmental processes. Inappropriate activation of this pathway leads to developmental defects and development of certain cancers. Upon Wnt signaling, beta-catenin binds TCF/LEF transcription factors. The TCF/LEF-beta-catenin complex then recruits a variety of transcriptional coactiv...
متن کاملBeta-catenin Forms Protein Aggregation at High Concentrations in HEK293TCells
Background: The canonical Wnt signal transduction (or the Wnt/β-catenin pathway) plays a crucial role in the development of animals and in carcinogenesis. Beta-catenin is the central component of this signaling pathway. The activation of Wnt/β-catenin signaling results in the cytoplasmic and nuclear accumulation of β-catenin. In the nucleus, β-catenin interacts with the TCF/LEF transcription fa...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Current Biology
دوره 9 شماره
صفحات -
تاریخ انتشار 1999