WikiPathways WP5609: Key metabolic pathways in melanoma, glycolytic pathway, TCA cycle, glutamine metabolism, and oxidative phosphorylation, with potential therapeutic targets and inhibitors. Inhibitors targeting critical metabolic nodes are outlined in teal. This pathway is based on Figure 1 in Shen et al.
WikiPathways WP5606: Cis- and trans-acting regulators shape gene expression within the β-globin cluster. The LDB1 complex (LDB1/LMO2/GATA1/TAL1) binds both the locus control region (LCR) and globin promoters, promoting chromatin looping to activate these genes—interactions that may be influenced by cis-acting variants linked to HbS haplotypes. Across the HBB gene cluster and its surrounding regions, BCL11A and ZBTB7A (LRF) binding sites are present, represented by red and blue stars. Each of these transcription factors recruits its own NuRD complex. MYB regulates HbF expression directly and also indirectly through KLF1 and BCL11A. Repression of the HbF genes is indicated by dashed lines. Inspired by figure 1 in Habara et al. (2017).
WikiPathways WP5604: This pathway shows the molecular pathophysiology of sickle cell disease. (A) A single–nucleotide variant in the β-globin gene replaces glutamic acid with valine at position 6 of the β-globin chain. Upon deoxygenation, the resulting hemoglobin S (HbS) molecules polymerize into rigid fibers, driving erythrocyte sickling (clockwise). (B) Sickled cells cause impaired blood rheology and enhanced adhesion of erythrocytes to neutrophils, platelets, and the endothelium, leading to slowed or obstructed microvascular flow – called vaso-occlusion. Vaso-occlusion in turn promotes ischemia-reperfusion (I-R) injury (clockwise). (C) HbS polymer formation also leads to red cell membrane damage and hemolysis (counterclockwise), releasing cell-free hemoglobin (Hb) into circulation. Oxygenated Hb (Fe²⁺) contributes to endothelial dysfunction by consuming nitric oxide (NO) and producing nitrate (NO₃⁻) and methemoglobin (Fe³⁺). Hb can also undergo Fenton chemistry with H₂O₂, generating hydroxyl radicals (•OH) and additional methemoglobin. Methemoglobin (Fe³⁺) can degrade and release cell-free heme (counterclockwise), a potent erythrocyte-derived DAMP. (D) ROS production, TLR4 activation, NET formation, release of tissue- or cell-derived DAMPs, extracellular DNA, and other yet-undefined mediators generated by cell-free heme or I-R injury can induce sterile inflammation by activating the inflammasome in vascular and immune cells, leading to IL-1β release.
WikiPathways WP5607: Erythroid lineage cell differentiation transitions from hematopoietic stem cells (HSCs) through successive erythroid progenitors – burst-forming unit–erythroid (BFU-E), colony-forming unit–erythroid (CFU-E) – then proerythroblasts (proEB), basophilic erythroblasts (basoEB), polychromatic erythroblasts (polyEB), and orthochromatic erythroblasts (orthoEB), then and ultimately to reticulocytes, pyrenocytes, and mature red blood cells (RBCs). Stage-specific transcription factors (GATA1, GATA2), surface markers (CD34, CD45, CD71, CD235a), the onset of hemoglobin expression, and other factors are also depicted.
December 2025 WikiPathways release: 840 edits by 8 contributors and 9 new pathways. Accessible via #webservices, #rstats, #pathvisio and #cytoscape.
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