How PML-RARa fusion proteins allow promyelocytes continued proliferation?
Best insight from top research papers
PML-RARa fusion proteins allow promyelocytes continued proliferation by stimulating transcription driven by HIF factors, which are critical regulators of adaptive responses to hypoxia and stem cell maintenance . Additionally, PML-RARa exploits a number of HIF-1a-regulated pro-leukemogenic functions, including cell migration, bone marrow neo-angiogenesis, and self-renewal of APL blasts . HIF-1a levels increase upon treatment of APL cells with all-trans retinoic acid (ATRA) . Inhibiting HIF-1a in APL mouse models delays leukemia progression and synergizes with ATRA to eliminate leukemia-initiating cells (LICs) . The PML-RARa fusion gene is the central leukemia-inducing lesion in APL and is directly targeted by ATRA and arsenic, both of which induce complete remissions . The blockage of ATRA signaling by PML-RARa is important for the pathogenesis of APL, considering the relevance of the ATRA signaling pathway for global hematopoiesis .
Answers from top 2 papers
More filters
| Papers (2) | Insight |
|---|---|
| PML-RARa fusion proteins stimulate transcription driven by HIF factors, which promote cell migration, angiogenesis, and self-renewal of APL blasts, allowing continued proliferation. | |
| The paper does not provide information on how PML-RARa fusion proteins allow promyelocytes continued proliferation. |
Related Questions
Does PM2.5 exposure alter the expression of genes involved in cell cycle regulation in kidney cell lines?5 answersExposure to PM2.5 has been shown to induce renal injury and early kidney damage in various studies. PM2.5 exposure leads to cytotoxicity, oxidative stress, and apoptosis in human proximal tubule epithelial cells (HK-2 cells). It also causes epithelial-mesenchymal transition (EMT) and activation of the IL-6/STAT3 pathway in HK-2 cells. Acute exposure to PM2.5 in rats results in increased blood pressure, early kidney damage biomarkers, oxidative stress, inflammation, and histological changes in the kidney. Subchronic exposure to PM2.5 in rats leads to renal histological lesions, pro-fibrotic state, angiotensin/bradykinin system imbalance, and immune and antioxidant imbalance. PM2.5 exposure also induces minimal abnormalities in the kidney, including fibrosis, mesangial expansion, and decreased glomerular and tubular lumen volumes. However, none of the abstracts specifically mention the alteration of genes involved in cell cycle regulation in kidney cell lines.
How PmrD connect PhoPQ and PmrAB?4 answersThe PmrD protein connects the PhoPQ and PmrAB two-component regulatory systems. In S. flexneri, a frameshift mutation in the pmrD gene disrupts the production of the functional PmrD protein, which leads to the loss of connection between the PhoPQ and PmrAB systems. This loss results in the abrogation of low Mg2+ mediated cationic antimicrobial peptide and polymyxin B resistance, while maintaining normal PmrAB-mediated polymyxin B resistance. On the other hand, S. sonnei maintains a functional PmrD protein and canonical signaling through this regulatory network. This species-specific gene loss suggests that S. flexneri and S. sonnei have evolved different regulatory responses to changing environmental conditions.
What is the role of Rab2 in the regulation of vesicle fusion?5 answersRab2 plays a crucial role in the regulation of vesicle fusion. It is involved in the delivery of presynaptic material from neuronal somata to synaptic terminals, ensuring successful synaptogenesis and neurotransmission. Rab2 is also recruited to late endosomal membranes, where it controls the fusion of biosynthetic carriers and lysosomes to late endosomes. Additionally, Rab2 is required for the fusion of autophagosomes to the endolysosomal pathway. These findings suggest that Rab2 is a central regulator of the endolysosomal and macroautophagic/autophagic pathways by controlling the major heterotypic fusion processes at the late endosome. Overall, Rab2 plays a critical role in vesicle fusion by facilitating the fusion of different types of vesicles and organelles, contributing to various cellular processes such as neurotransmitter release and endolysosomal trafficking.
What is the function of Rabep2?4 answersRabep2 is a gene that plays a role in ischemic stroke outcomes and vascular endothelial cell function. It has been identified as a causal gene for regulating cerebral infarct volume and collateral vessel number in ischemic stroke. Rabep2 interacts with the small GTPase Rab4 and regulates VEGFR2 endosomal trafficking, maintaining cell-surface expression of VEGFR2 and VEGF signaling. Additionally, Rabep2 is a substrate of glycogen synthase kinase-3 (GSK3) and its phosphorylation at Ser200 is enhanced by prior phosphorylation at Ser204, making it a potential biomarker for GSK3 activity. Rabep2 also plays a role in the recycling of endocytosed active β1 integrins to the plasma membrane, affecting focal adhesion formation, cell migration, and cancer cell invasion.
What is the function of Rab7?5 answersRab7 is a small GTPase that plays a crucial role in various cellular processes, including vesicular trafficking, endosome maturation, lysosome function, autophagy, apoptosis, signaling, and cell migration. It is involved in maintaining cellular health and regulating the endosome-lysosome system. Rab7 is important for the transport of material to the lysosome, lysosomal biogenesis, and fusion of late endosomes and lysosomes. It also regulates the autophagic pathway and is essential for autolysosome maturation. In addition, Rab7 has been shown to play a role in the innate immune system, antimicrobial function, and the expression of antimicrobial peptides. The function of Rab7 is complex and varies depending on the cellular context and environmental factors. Understanding the role of Rab7 is important for studying diseases such as pulmonary arterial hypertension and cancer, and for developing potential therapeutic strategies.
How PML-RARA activates downstream signaling pathways involved in cell survival and proliferation in acute promyelocytic leukemia?5 answersPML-RARA fusion protein, resulting from the t(15;17) translocation, plays a critical role in the pathogenesis of acute promyelocytic leukemia (APL) by repressing retinoic acid-inducible genes involved in myeloid differentiation. Dysregulation of these genes leads to abnormal signaling, which allows pre-leukemic cells to evade differentiation controls. Treatment of APL cells with retinoic acid induces up-regulation of these genes, which are dominantly repressed by PML-RARA, and is required for reactivation of the differentiation program. The PML-RARA fusion gene and its isoforms have been characterized using RT/PCR, and their biological activity needs further exploration. The identification of these genes and the signaling pathways interrupted during leukemia transformation and reactivated during retinoic acid-induced differentiation will contribute to the development of new molecular targets for APL treatment.