A5061680926- Pluripotent Stem Cells Research
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Hereditary Neurological Disorders
- Parkinson's Disease Mechanisms and Treatments
- Protein Tyrosine Phosphatases
- ATP Synthase and ATPases Research
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
- Nuclear Receptors and Signaling
- AI in cancer detection
- Cell death mechanisms and regulation
- Polyamine Metabolism and Applications
- Caveolin-1 and cellular processes
- Electrochemical Analysis and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA modifications and cancer
- Tuberous Sclerosis Complex Research
- Cancer Mechanisms and Therapy
- Trace Elements in Health
- Fungal Plant Pathogen Control
- Biochemical and biochemical processes
Universitat de València
2012-2024
INCLIVA Health Research Institute
2017-2023
Anthrologica
2020
Wellcome/MRC Cambridge Stem Cell Institute
2008-2012
University of Cambridge
2012
Centro de Investigacion Principe Felipe
2005-2006
Instituto Valenciano de Investigaciones Agrarias
1999-2004
The tumor suppressor phosphatase PTEN regulates cell migration, growth, and survival by dephosphorylating phosphatidylinositol second messengers signaling phosphoproteins. possesses a C-terminal noncatalytic regulatory domain that contains multiple putative phosphorylation sites, which could play an important role in the control of its biological activity. protein kinase CK2 phosphorylated, constitutive manner, cluster Ser/Thr residues located at C terminus. PTEN-phosphorylated defective...
Abstract During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither importance remodelling for cell reprogramming, nor molecular mechanisms controlling this are well understood. Here, we show that an early wave fragmentation occurs upon expression factors. Reprogramming-induced fission is minor decrease in mass but not mitophagy. The...
The tumor suppressor phosphatase PTEN is a key regulator of cell growth and apoptosis that interacts with PDZ domains from regulatory proteins, including MAGI-1/2/3, hDlg, MAST205. Here we identified novel PTEN-binding within the MAST205-related syntrophin-associated serine/threonine kinase MAST3, characterized regions involved in its interaction distinctive domains, analyzed functional consequences on domain binding. Using panel mutations, as well chimeras containing distinct related...
Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm an inactive form by association through a kinase interaction motif (KIM) and dephosphorylation. The related phosphatases STEP were phosphorylated cAMP-dependent A (PKA). PKA phosphorylation site on was identified as Ser231 residue, located within KIM. Upon of Ser231, binding dephosphorylation MAP extracellular signal–regulated (ERK)1/2 p38α impaired. Furthermore, treatment COS-7 cells with...
The targeting of the tumor suppressor PTEN protein to distinct subcellular compartments is a major regulatory mechanism function, by controlling its access substrates and effector proteins. Here, we investigated molecular basis functional consequences nuclear/cytoplasmic distribution. accumulated in nucleus cells treated with apoptotic stimuli. Nuclear accumulation was enhanced mutations motifs domains, it dependent on an N-terminal nuclear localization domain. Coexpression dominant negative...
PTEN phosphatase is one of the most commonly targeted tumor suppressors in human cancers and a key regulator cell growth apoptosis. We have found that cleaved by caspase-3 at several target sites, located unstructured regions within C terminus molecule. Cleavage was increased upon TNFα-cell treatment negatively regulated phosphorylation C-terminal tail protein kinase CK2. The proteolytic fragments displayed reduced stability, their capability to interact with interacting scaffolding...
ERK1 and ERK2 associate with the tyrosine phosphatase PTP-SL through a kinase interaction motif (KIM) located in juxtamembrane region of PTP-SL. A glutathioneS-transferase (GST)-PTP-SL fusion protein containing KIM associated as well p38/HOG, but not related JNK1 or C. Accordingly, showed vitro substrate specificity to phosphorylate GST-PTP-SL comparison GST-c-Jun. Furthermore, dephosphorylation by PTP-SLΔKIM mutant was impaired. Thein association ERK1/2 highly stable; however, low...
The ability to direct differentiation of mouse embryonic stem (ES) cells into specific lineages not only provides new insights the pathways that regulate lineage selection but also has translational applications, for example in drug discovery. We set out develop a method differentiating ES mesodermal at high efficiency without first having induce embryoid body formation. were plated on feeder layer PA6 cells, which have membrane-associated stromal-derived inducing activity (SDIA), molecular...
We have recently shown that mitochondrial fission is induced early in reprogramming a Drp1-dependent manner; however, the identity of factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used panel RNAi targeting involved regulation dynamics and observed MiD51, Gdap1 and, lesser extent, Mff were found play key roles this process. Cells derived from Gdap1-null mice further explore role factor cell reprogramming. Microarray data revealed prominent...
Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- glycolytic-based metabolism. However, neither the dynamics nor factors controlling this are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes robust bivalent energetics program early in cell reprogramming. Cells prone undergo exhibit high mitochondrial membrane potential display hybrid We conclude MYC proteins...
Charcot-Marie-Tooth disease is a chronic hereditary motor and sensory polyneuropathy targeting Schwann cells and/or neurons. Its multifactorial polygenic origin portrays complex clinical phenotype of the with wide range genetic inheritance patterns. The disease-associated gene GDAP1 encodes for mitochondrial outer membrane protein. Mouse insect models mutations in Gdap1 have reproduced several traits human disease. However, precise function cell types affected by remains unknown. Here, we...
Abstract Somatic cells can be reprogrammed to induced pluripotent stem (iPS) by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated role Gata4 in reprogramming process present evidence for a negative this family transcription induction pluripotency. Coexpression with Sox2 or without Myc mouse embryonic fibroblasts greatly impaired endogenous Nanog expression. The lack upregulation was associated blockade transition from initiation phase full state...
Dopamine replacement represents the standard therapy for Parkinson's disease (PD), a common, chronic, and incurable neurological disorder; however, this approach only treats symptoms of devastating disease. In search novel disease-modifying therapies that target other relevant molecular cellular mechanisms, Drosophila has emerged as valuable tool to study neurodegenerative diseases due presence complex central nervous system, blood–brain barrier, similar neurotransmitter profile humans....
Several studies have reported the direct conversion of mouse fibroblasts to hepatocyte-like cells with different degrees maturation by expression hepatic fate-conversion factors.We used a combination lentiviral vectors expressing factors Oct4, Sox2, Klf4, and Myc convert embryonic into cells.We generated progenitor-like features (iHepL cells). iHepL displayed basic hepatocyte functions but failed perform characteristic mature hepatocytes such as significant Cyp450 or urea cycle activities....
Metabolic rewiring and mitochondrial dynamics remodelling are hallmarks of cell reprogramming, but the roles reprogramming factors in these changes not fully understood. Here we show that c-MYC induces biosynthesis fatty acids increases rate pentose phosphate pathway. Time-course profiling complex lipids during using lipidomics revealed a profound lipid content, as well saturation length their acyl chains, c-MYC-dependent manner. Pluripotent cells displayed abundant cardiolipins scarce...
Human CMT2-FiPS4F1 cell line was generated from fibroblasts of a patient with Charcot-Marie-Tooth disease harbouring the following mutations in GDAP1 gene heterozygosis: p.Q163X/p.T288NfsX3. This did not present PM22, MPZ or GJB genes. reprogramming factors OCT3/4, KLF4, SOX2 and C-MYC were delivered using non-integrative methodology that involves use Sendai virus.
Abstract Zinc is a critical ion for large number of cellular functions. In the central nervous system, zinc ions are involved in synaptic transmission. Therefore, homeostasis essential, and cells have developed variety mechanisms to control concentration, including zincosome formation. Alterations free levels been associated with brain dysfunction present many illnesses syndromes. Astrocytes implicated maintenance neuronal milleu homeostasis. this work, we analyzed combination direct (TSQ)...