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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/219842
CPEB1 and CPEB4 in skin homeostasis and tumorigenesis
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[eng] The skin epidermis is a continuously renewing tissue that requires a tightly regulated balance between keratinocyte proliferation and terminal differentiation to ensure proper structure and function. Despite substantial progress in characterizing the epigenomic and transcriptional regulatory mechanisms, the intricate control of epidermal homeostasis is still not fully understood. Emerging evidence is beginning to unveil the important role of post-transcriptional regulation by RNA-binding proteins, providing an additional layer of gene expression control essential for maintaining epidermal homeostasis and influencing skin tumor development.
Cytoplasmic Polyadenylation Element Binding Proteins (CPEBs) are a family of four RNA-binding proteins (CPEB1-4) that regulate mRNA translation and stability by dynamically modulating the poly(A) tail length of specific mRNA targets. Although initially discovered during meiotic maturation, CPEBs have also been identified in somatic cells, extending their role beyond meiosis. However, CPEB1 and CPEB4 have not been examined together in the context of epidermal homeostasis, and their specific contributions to this tissue remain unknown.
In this work, we have characterized the roles of CPEB1 and CPEB4 in keratinocytes and the interfollicular epidermis. Our findings reveal opposing functions of CPEB1 and CPEB4 in epidermal homeostasis and skin tumorigenesis. We have identified their mRNA targets in keratinocytes and uncovered a novel and contrasting role of CPEB1 and CPEB4 in keratinocyte differentiation. Both proteins are upregulated during keratinocyte differentiation and mediate a specific post-transcriptional control that fine-tunes cellular profiles toward either proliferation or differentiation. Notably, by focusing on the Notch signaling pathway, we found that the deletion of CPEB1 and CPEB4 in keratinocytes results in opposing patterns of Notch activation, which correlate with distinct keratinocyte differentiation states.
Altogether, our results provide mechanistic insights into how CPEB1 and CPEB4 are involved in keratinocyte differentiation, potentially through the modulation of Notch signaling. This study further underscores the relevance of post-transcriptional regulation by RNA-binding proteins in maintaining tissue homeostasis and offers new perspectives on the role of CPEBs in skin biology.
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FERRER CAELLES, Anna. CPEB1 and CPEB4 in skin homeostasis and tumorigenesis. [consulta: 26 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/219842]