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Hypoxia Inducible Factor-1 beta and Cancer Development

Hypoxia inducible factor-1 (HIF-1) is a major transcription factor that is composed of two subunits: HIF-1 alpha and HIF-1 beta, the latter being a constitutively-expressed aryl hydrocarbon receptor nuclear transporter (ARNT).

Identifying JARID2 in Embryo Development

The jumonji (JMJ) gene, obtained by a gene trap strategy, is essential for embryogenesis and is suggested to play important roles in cell growth during development. The amino acid sequence of the JMJ protein includes a nuclear localization signal and a DNA binding motif called the AT-rich interactive domain (ARID). Unlike the other members of the JARID family of proteins, JARID2 has a long N-terminal moiety devoid of characterized domains.

Aches & Pains: Aggrecan in Joint Disease and Osteoarthritis

Aggrecan is essential for the normal function of articular cartilage and intervertebral discs. Aggrecan provides the ability for the tissues to withstand compressive loading. This property is dependent on both the high charge density endowed by its numerous chondroitin and keratan sulfate chains and its ability to form large molecular aggregates interacting with hyaluronans. Degradation of Aggrecan via the action of proteases takes place throughout life and the degradation products which accumulate in the tissue and impair its function.

No Monkey Business: APE1 is a Critical DNA Repair Enzyme

APE1 (aka. HAP1, /Ref-1 or APEX) the mammalian ortholog of Escherichia coli Xth is a multifunctional protein possessing both DNA repair and transcriptional regulatory activity. APE1 acts essentially as master regulator of controlling cellular response to oxidative stress, and contributes to the genome stability (1).

HIF Prolyl Hydroxylase 2: an important Oxygen Sensor Protein

Prolyl hydroxylase domain (PHD) proteins, including PHD1, PHD2, and PHD3, mediate oxygen-dependent degradation of hypoxia-inducible factor (HIF) alpha subunits. Suppression of PHD enzymes leads to stabilization of HIFs and offers a potential treatment option for many ischemic disorders, such as peripheral artery occlusive disease, myocardial infarction, and stroke (1).

Jumonji domain-containing protein 3 (JMJD3) a Histone H3K27 Demethylase

Jumonji domain-containing protein 3 (JMJD3), identified as H3K27me3 demethylase, controls the expression of key regulators and markers of neurogenesis, and is required for commitment to the neural lineage. Nevertheless, the precise molecular targets of JMJD3 remain largely uncharacterized. The regulation of JMJD3 appears to be highly gene- and context- specific, suggesting interplay with specific molecules to promote fine-tuning more than the on/off alternation of methylation status.

Glucose Transporter 1 (GLUT1): a Key Metabolic Neuronal Player

Glucose is the principal fuel source for the brain and GLUT1 is the only vehicle by which glucose enters the brain. In case of GLUT1 deficiency, the risk of clinical manifestations is increased in infancy and childhood, when the brain glucose demand is maximal.

Dynamin-related Protein 1 (DRP1) in Mitochondria and Apoptosis.

Dynamin-related Protein 1 (DRP1) is known to function in mitochondrial and peroxisomal division and mediate membrane fission through oligomerization into ring-like structure and sever the mitochondrial membrane, through a GTP hydrolysis-dependent mechanism.

IRE1 alpha and ER Stress: Keys to Disease Progression Pathways

Inositol Requiring Enzyme 1 alpha (IRE1 alpha) is a transmembrane-RNase with an endoplasmic reticulum (ER) luminal sensor domain and cytosolic kinase and ribonuclease domains. IRE1 also plays a central role in the ER stress response (1).

CIP2A: The Cancerous Inhibitor of Protein Phosphatase 2A

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