From head to toes: the multiple facets of Sox proteins.
Ontology highlight
ABSTRACT:
SUBMITTER: Wegner M
PROVIDER: S-EPMC148332 | biostudies-other | 1999 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The Citron protein was originally identified for its capability to specifically bind the active form of RhoA small GTPase, leading to the simplistic hypothesis that it may work as a RhoA downstream effector in actin remodeling. More than two decades later, a much more complex picture has emerged. In particular, it has become clear that in animals, and especially in mammals, the functions of the Citron gene (CIT) are intimately linked to many aspects of central nervous system (CNS) development and function, although the gene is broadly expressed. More specifically, CIT encodes two main isoforms, Citron-kinase (CIT-K) and Citron-N (CIT-N), characterized by complementary expression pattern and different functions. Moreover, in many of their activities, CIT proteins act more as upstream regulators than as downstream effectors of RhoA. Finally it has been found that, besides working through actin, CIT proteins have many crucial functional interactions with the microtubule cytoskeleton and may directly affect genome stability. In this review, we will summarize these advances and illustrate their actual or potential relevance for CNS diseases, including microcephaly and psychiatric disorders.
| S-EPMC7053930 | biostudies-literature
Project description:Over 10 years have passed since the first Sox gene was implicated in melanocyte development. Since then, we have discovered that SOX5, SOX9, SOX10 and SOX18 all participate as transcription factors that affect key melanocytic genes in both regulatory and modulatory fashions. Both SOX9 and SOX10 play major roles in the establishment and normal function of the melanocyte; SOX10 has been shown to heavily influence melanocyte development and SOX9 has been implicated in melanogenesis in the adult. Despite these advances, the precise cellular and molecular details of how these SOX proteins are regulated and interact during all stages of the melanocyte life cycle remain unknown. Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma.
| S-EPMC2906668 | biostudies-literature
Project description:Structural Maintenance of Chromosomes (SMCs) are part of a large family of ring complexes that participates in a number of DNA transactions. Among SMCs, SMC1A gene is unique. It encodes a subunit of the cohesin-core complex that tethers sister chromatids together to ensure correct chromosome segregation in both mitosis and meiosis. As a member of the cohesin ring, SMC1A takes part in gene transcription regulation and genome organization; and it participates in the DNA Damage Repair (DDR) pathway, being phosphorylated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3 Related (ATR) threonine/serine kinases. It is also a component of the Recombination protein complex (RC-1) involved in DNA repair by recombination. SMC1A pathogenic variants have been described in Cornelia de Lange syndrome (CdLS), a human rare disease, and recently SMC1A variants have been associated with epilepsy or resembling Rett syndrome phenotype. Finally, SMC1A variants have been identified in several human cancers. In this review, our current knowledge of the SMC1A gene has been summarized.
| S-EPMC8011328 | biostudies-literature
Project description:Ubiquitination plays a pivotal role in several cellular processes and is critical for protein degradation and signaling. E3 ubiquitin ligases are the matchmakers in the ubiquitination cascade, responsible for substrate recognition. In order to achieve selectivity and specificity on their substrates, HECT E3 enzymes are tightly regulated and exert their function in a spatially and temporally controlled fashion in the cells. These characteristics made HECT E3s intriguing targets in drug discovery in the context of cancer biology.
| S-EPMC6457168 | biostudies-literature
Project description:SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, by ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA regions strongly enriched for Nfi binding motifs. Oligodendrocyte genes instead are prebound by SOX9 only, at sites which during oligodendrocyte maturation are targeted by SOX10. Interestingly, reporter gene assays and functional studies in the spinal cord reveal that SOX3 binding represses the synergistic activation of astrocyte genes by SOX9 and NFIA, whereas oligodendrocyte genes are activated in a combinatorial manner by SOX9 and SOX10. These genome-wide studies demonstrate how sequentially expressed SOX proteins act on lineage-specific regulatory DNA elements to coordinate glial gene expression both in a temporal and in a sub-lineage-specific fashion.
| S-EPMC6216240 | biostudies-literature
Project description:IntroductionTwo established subjective memory decline facets (SMD; complaints, concerns) are early indicators of memory decline and Alzheimer's disease. We report (1) a four-facet SMD inventory (memory complaints, concerns, compensation, self-efficacy) and (2) prediction of memory change and moderation by sex.MethodsThe longitudinal design featured 40 years (53 to 97) of non-demented aging (n = 580) from the Victoria Longitudinal Study. Statistical analyses included confirmatory factor analyses and conditional latent growth modeling.ResultsThe four-facet SMD Inventory was psychometrically confirmed. Longitudinal analyses revealed significant variability in level and change for SMD and memory. Prediction analyses showed complaints and concerns predicted lower level and steeper memory decline; however, follow-up moderation analyses revealed selective predictions for females. Memory compensation predicted decline overall. Lower memory self-efficacy predicted steeper decline selectively for males.DiscussionAlthough traditional and novel SMD facets predicted memory decline, differential sex moderation was observed. SMD research benefits from conceptual complementarity and precision prediction.
| S-EPMC7447903 | biostudies-literature
Project description:BackgroundInborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans.ObjectiveWe sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency.MethodsWe assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells.ResultsSOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients.ConclusionsSOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.
| S-EPMC8375263 | biostudies-literature
Project description:Eccrine sweat glands, which are distributed over the whole bodies of primates and humans, have long been regarded mainly to have a function in thermoregulation. However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate immune defense of human skin against infection. In the meantime, a number of studies proved the importance of dermcidin in skin host defense. Several reports also state that peptides processed from the dermcidin precursor protein exhibit a range of other biological functions in neuronal and cancer cells. This review summarizes the evidence gathered until now concerning the expression of dermcidin and the functional relevance of dermcidin-derived peptides.
| S-EPMC6741627 | biostudies-literature
Project description:Nitrogen (N) is a gas and the fifth most abundant element naturally found in the atmosphere. N's role in agriculture and plant metabolism has been widely investigated for decades, and extensive information regarding this subject is available. However, the advent of sequencing technology and the advances in plant biotechnology, coupled with the growing interest in functional genomics-related studies and the various environmental challenges, have paved novel paths to rediscovering the fundamentals of N and its dynamics in physiological and biological processes, as well as biochemical reactions under both normal and stress conditions. This work provides a comprehensive review on multiple facets of N and N-containing compounds in plants disseminated in the literature to better appreciate N in its multiple dimensions. Here, some of the ancient but fundamental aspects of N are revived and the advances in our understanding of N in the metabolism of plants is portrayed. It is established that N is indispensable for achieving high plant productivity and fitness. However, the use of N-rich fertilizers in relatively higher amounts negatively affects the environment. Therefore, a paradigm shift is important to shape to the future use of N-rich fertilizers in crop production and their contribution to the current global greenhouse gases (GHGs) budget would help tackle current global environmental challenges toward a sustainable agriculture.
| S-EPMC9410007 | biostudies-literature
Project description:The synthesis of high energy facets and tunable low energy facets was achieved in CeO2 films on a SrTiO3 substrate by pulsed laser deposition. Three different facets of CeO2 with distinctive morphologies appeared consecutively. Firstly, the (100) facet of CeO2, which is the highest energy surface, was grown on the SrTiO3 (STO) (100) substrate. The surface energy was decreased gradually with the increase of the laser pulse shots, and the (110) and (111) LEF appeared consecutively. The three different facets presented distinctive morphologies and the interface between each facet could be easily observed by the cross section of Transmission Electron Microscope (TEM) imaging. The interface between the (100) and (110) facet may exhibit excellent oxygen storage capacity, even better than the (100) facet.
| S-EPMC9048269 | biostudies-literature