scholarly journals The Role of Caspase-2 in Regulating Cell Fate

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1259
Author(s):  
Vasanthy Vigneswara ◽  
Zubair Ahmed
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Comprehensive Overview ◽  
Cellular Processes ◽  
Evolutionarily Conserved ◽  
Caspase Family ◽  
A Cell ◽  
Caspase 2 ◽  
Cycle Regulation

Caspase-2 is the most evolutionarily conserved member of the mammalian caspase family and has been implicated in both apoptotic and non-apoptotic signaling pathways, including tumor suppression, cell cycle regulation, and DNA repair. A myriad of signaling molecules is associated with the tight regulation of caspase-2 to mediate multiple cellular processes far beyond apoptotic cell death. This review provides a comprehensive overview of the literature pertaining to possible sophisticated molecular mechanisms underlying the multifaceted process of caspase-2 activation and to highlight its interplay between factors that promote or suppress apoptosis in a complicated regulatory network that determines the fate of a cell from its birth and throughout its life.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

2020 ◽  
Vol 21 (7) ◽  
pp. 2576 ◽  
Author(s):  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
Elisabetta Chiaradia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Communication ◽  
Lysosomal Storage ◽  
Cellular Processes ◽  
Age Related ◽  
Extracellular Release ◽  
A Cell ◽  
Endosomal System

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.

ON SIMULATING THE GENERATION OF MOSAICISM DURING MAMMALIAN CEREBRAL CORTICAL DEVELOPMENT

2009 ◽  
Vol 17 (01) ◽  
pp. 27-62 ◽  
Author(s):  
MICHAEL A. CASE ◽  
HUGH R. MACMILLAN
Keyword(s):  
Decision Making ◽  
Single Cell ◽  
Cell Fate ◽  
Cell Population ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Cortical Development ◽  
Coarse Grained ◽  
Biological Organization ◽  
Cellular Processes

Renewed calls for a systems biology reflect the hope hat enduring biological questions at single-cell and cell-population scales will be resolved as modern molecular biology, with its reductionist program, approaches a nearly-complete characterization of the molecular mechanisms of specific cellular processes. Due to the confounding complexity of biological organization across these scales, computational science is sought to complement the intuition of experimentalists. However, with respect to the molecular basis of cellular processes during development and disease, a gulf between feasible simulations and realistic biology persists. Formidable are the mathematical and computational challenges to conducting and validating cell population-scale simulations, drawn from single-cell level and molecular level details. Nonetheless, in some biological contexts, a focus on core processes crafted by evolution can yield coarse-grained mathematical models that retain explanatory potential despite drastic simplification of known biochemical kinetics. In this article, we bring this modeling philosophy to bear on the nature of neural progenitor cell decision making during mammalian cerebral cortical development. Specifically, we present the computational component to a research program addressing developmental links between (i) the cellular response to endogenous DNA damage, (ii) primary mechanisms of neuronal genetic heterogeneity, or mosaicism, and (iii) the cell fate decision making that defines the population kinetics of neurogenesis.

scholarly journals Homodimerization of Nemo-like kinase is essential for activation and nuclear localization

2011 ◽  
Vol 22 (2) ◽  
pp. 266-277 ◽  
Author(s):  
Shizuka Ishitani ◽  
Kenji Inaba ◽  
Kunihiro Matsumoto ◽  
Tohru Ishitani
Keyword(s):  
Transcription Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Nuclear Localization ◽  
Biochemical Analysis ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Cellular Processes ◽  
Evolutionarily Conserved

Nemo-like kinase (NLK) is an evolutionarily conserved protein kinase that phosphorylates several transcription factors. However, the molecular mechanisms that regulate NLK activity have been poorly understood. Here we show that homodimerization of NLK is required for its activation and nuclear localization. Biochemical analysis revealed that NLK is activated through intermolecular autophosphorylation of NLK dimers at Thr-286. Mutation of NLK at Cys-425, which corresponds to the defect in the Caenorhabditis elegans NLK homologue lit-1, prevented NLK dimerization, rendering NLK defective in both nuclear localization and kinase activity. By contrast, the external addition of nerve growth factor, which has been previously identified as an NLK activator, induced dimerization and Thr-286 autophosphorylation of endogenous NLK proteins. In addition, both dimerization and Thr-286 phosphorylation of NLK were found to be essential for induction of neurite-like cellular processes by NLK. The present findings suggest that dimerization is an initial key event required for the functional activation of NLK.

scholarly journals DAXX Is a Crucial Factor for Proper Development of Mammalian Oocytes and Early Embryos

2021 ◽  
Vol 22 (3) ◽  
pp. 1313
Author(s):  
Irina Bogolyubova ◽  
Dmitry Bogolyubov
Keyword(s):  
Tandem Repeats ◽  
Cellular Proliferation ◽  
Death Domain ◽  
Multifunctional Protein ◽  
Cellular Processes ◽  
Epigenetic Modifiers ◽  
Early Embryos ◽  
Evolutionarily Conserved ◽  
Induced Apoptosis ◽  
Cycle Regulation

The Death-domain associated protein 6 (DAXX) is an evolutionarily conserved and ubiquitously expressed multifunctional protein that is implicated in many cellular processes, including transcription, cellular proliferation, cell cycle regulation, Fas-induced apoptosis, and many other events. In the nucleus, DAXX interacts with transcription factors, epigenetic modifiers, and chromatin-remodeling proteins such as the transcription regulator ATRX—the α-thalassemia/mental retardation syndrome X-linked ATP-dependent helicase II. Accordingly, DAXX is considered one of the main players involved in chromatin silencing and one of the most important factors that maintain integrity of the genome. In this brief review, we summarize available data regarding the general and specific functions of DAXX in mammalian early development, with special emphasis on the function of DAXX as a chaperone of the histone variant H3.3. Since H3.3 plays a key role in the developmental processes, especially in the pronounced rearrangements of heterochromatin compartment during oogenesis and embryogenesis, DAXX can be considered as an important factor supporting proper development. Specifically, loss of DAXX affects the recruitment of ATRX, transcription of tandem repeats and telomere functions, which results in a decrease in the viability of early embryos.

scholarly journals Validation of commercial ERK antibodies against the ERK orthologue of the scleractinian coral Stylophora pistillata

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 577
Author(s):  
Lucile Courtial ◽  
Vincent Picco ◽  
Gilles Pagès ◽  
Christine Ferrier-Pagès
Keyword(s):  
Cell Fate ◽  
Cell Cycle Regulation ◽  
Signalling Pathway ◽  
Immune Reactivity ◽  
Cell Fate Determination ◽  
Stylophora Pistillata ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Living Organisms ◽  
Cycle Regulation

The extracellular signal-regulated protein kinase (ERK) signalling pathway controls key cellular processes, such as cell cycle regulation, cell fate determination and the response to external stressors. Although ERK functions are well studied in a variety of living organisms ranging from yeast to mammals, its functions in corals are still poorly known. The present work aims to give practical tools to study the expression level of ERK protein and the activity of the ERK signalling pathway in corals. The antibody characterisation experiment was performed five times and identical results were obtained. The present study validated the immune-reactivity of commercially available antibodies directed against ERK and its phosphorylated/activated forms on protein extracts of the reef-building coral Stylophora pistillata.

scholarly journals Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vincenza Simona Delvecchio ◽  
Claudia Fierro ◽  
Sara Giovannini ◽  
Gerry Melino ◽  
Francesca Bernassola
Keyword(s):  
Hematological Malignancies ◽  
Apoptotic Cell ◽  
Ubiquitin Ligases ◽  
Covalent Attachment ◽  
E3 Ubiquitin Ligases ◽  
Comprehensive Overview ◽  
Altered Expression ◽  
Hect Domain ◽  
Cellular Processes ◽  
Substrate Proteins

AbstractUbiquitination-mediated proteolysis or regulation of proteins, ultimately executed by E3 ubiquitin ligases, control a wide array of cellular processes, including transcription, cell cycle, autophagy and apoptotic cell death. HECT-type E3 ubiquitin ligases can be distinguished from other subfamilies of E3 ubiquitin ligases because they have a C-terminal HECT domain that directly catalyzes the covalent attachment of ubiquitin to their substrate proteins. Deregulation of HECT-type E3-mediated ubiquitination plays a prominent role in cancer development and chemoresistance. Several members of this subfamily are indeed frequently deregulated in human cancers as a result of genetic mutations and altered expression or activity. HECT-type E3s contribute to tumorigenesis by regulating the ubiquitination rate of substrates that function as either tumour suppressors or oncogenes. While the pathological roles of the HECT family members in solid tumors are quite well established, their contribution to the pathogenesis of hematological malignancies has only recently emerged. This review aims to provide a comprehensive overview of the involvement of the HECT-type E3s in leukemogenesis.

scholarly journals OXPHOS Promotes Apoptotic Resistance and Persistence in TH17 cells

2021 ◽  
Author(s):  
Hanna S. Hong ◽  
Nneka E. Mbah ◽  
Mengrou Shan ◽  
Kristen Loesel ◽  
Lin Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cell Fate ◽  
Apoptotic Cell ◽  
Metabolic Phenotype ◽  
Tumor Studies ◽  
A Cell

AbstractApoptotic cell death is a cell-intrinsic, immune tolerance mechanism that regulates the magnitude and resolution of T cell-mediated responses. Evasion of apoptosis is critical for the generation of memory T cells, as well as autoimmune T cells, and knowledge of the mechanisms that enable resistance to apoptosis will provide insight into ways to modulate their activity during protective and pathogenic responses. IL-17-producing CD4 T cells (TH17s) are long-lived, memory cells. These features enable their role in host defense, chronic inflammatory disorders, and anti-tumor immunity. A growing number of reports now indicate that TH17s in vivo require mitochondrial oxidative phosphorylation (OXPHOS), a metabolic phenotype that is poorly induced in vitro. To elucidate the role of OXPHOS in TH17 processes, we developed a system to polarize TH17s that metabolically resembled their in vivo counterparts. We discovered that directing TH17s to use OXPHOS promotes mitochondrial fitness, glutamine anaplerosis, and an anti-apoptotic phenotype marked by high BCL-XL and low BIM. Through competitive co-transfer experiments and tumor studies, we further revealed how OXPHOS protects TH17s from cell death while enhancing their persistence in the periphery and tumor microenvironment. Together, our work demonstrates a non-classical role of metabolism in regulating TH17 cell fate and highlights the potential for therapies that target OXPHOS in TH17-driven diseases.

scholarly journals Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes

2021 ◽  
Author(s):  
Martin Kinisu ◽  
Yong Jin Choi ◽  
Claudia Cattoglio ◽  
Ke Liu ◽  
Hector Roux de Bezieux ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Endogenous Retroviruses ◽  
Preimplantation Embryos ◽  
Cell State ◽  
Upstream Regulator ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
Dual Activation ◽  
Transcription Program

SummaryEarly blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable of generating both embryonic and extra-embryonic lineages in blastocysts. Here, we identified three major 2 cell (2C) specific endogenous retroviruses (ERVs) as the molecular hallmark of the bi-potential plasticity. Using the LTRs of all three 2C-ERVs, we identified Klf5 as their major upstream regulator. Klf5 is essential for bi-potential cell fate: a single Klf5-overexpressing ESC generated terminally differentiated embryonic and extra-embryonic lineages in chimeric embryos, and Klf5 directly induces both ICM and TE specification genes. Intriguingly, Klf5 and Klf4 act redundantly during ICM specification, whereas Klf5 deficiency alone impairs TE specification. Klf5 is regulated by multiple 2C-specific transcription factors, particularly Dux, and the Dux/Klf5 axis is evolutionarily conserved. Altogether, the 2C-specific transcription program converges on Klf5 to establish bi-potential cell fate, enabling a cell state with dual activation of ICM and TE genes.

scholarly journals Engineering Cell Fate: The Roles of iPSC Transcription Factors, Chemicals, Barriers and Enhancing Factors in Reprogramming and Transdifferentiation

2015 ◽  
Author(s):  
Behnam Ebrahimi
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Viral Vectors ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Direct Reprogramming ◽  
Comprehensive Overview ◽  
Ips Cell ◽  
Chemical Reprogramming

Direct reprogramming technology has emerged as an outstanding technique for the generation of induced pluripotent stem (iPS) cells and various specialized cells directly from somatic cells of different species. Recent studies dissecting the molecular mechanisms of reprogramming have methodologically improved the quality, ease and efficiency of reprogramming and eliminated the need for genome modifications with integrating viral vectors. With these advancements, direct reprogramming technology has moved closer to clinical application. Here, we provide a comprehensive overview of the cutting-edge findings regarding distinct barriers of reprogramming to pluripotency, strategies to enhance reprogramming efficiency, and chemical reprogramming as one of the non-integrating approaches in iPS cell generation. In addition to direct transdifferentiation, pluripotency factor-induced transdifferentiation or cell activation and signaling directed (CASD) lineage conversion is described as a robust strategy for the generation of both tissue-specific progenitors and clinically relevant cell types. Then, we consider the possibility that a combined method of inhibition of roadblocks (e.g. p53, p21, p57, Mbd3, etc.), and application of enhancing factors in a chemical reprogramming paradigm would be a safe, reliable and effective approach in pluripotent reprogramming and transdifferentiation. Furthermore, with respect to the state of native, aberrant, and target gene regulatory networks in reprogrammed cell populations, CellNet is reviewed as a computational platform capable of evaluating the fidelity of reprogramming methods and refining current engineering strategies. Ultimately, we conclude that a faithful, highly efficient and integration-free reprogramming paradigm would provide powerful tools for research studies, drug-based induced regeneration, cell transplantation therapies and other regenerative medicine purposes.

Sign in / Sign up

Export Citation Format

Share Document