title: Advances in understanding the pathogenesis of primary familial and congenital polycythaemia.
abstract: Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA. Lily.Huang@utsouthwestern.edu
authors.forename: Lily J
authors.initials: LJ
authors.lastname: Huang
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Shen
authors.forename: Gamze B
authors.initials: GB
authors.lastname: Bulut
mesh_terms: D015536:Down-Regulation; D006801:Humans; D009154:Mutation; D011086:Polycythemia / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017467:Receptors, Erythropoietin