Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors

Abstract

The earliest second messenger discovered was the CAMP. cAMP weakly penetrates into the cell. O n the other hand, dibutyryl cAMP is membrane-penetratible derivative of the CAMP, which shows high activity and at present time is largerly used in experiments.The comparative study of the effects of cAMP and dibutyryl cAMP on the structure of monoolein-water cubic liquid-crystalline phase have been performed by X-ray diffraction, Raman, and FTIR spectroscopies. Based on the X-ray diffraction data it was established that cAMP does not change the structure of Pn3m lattice, contrary to dibutyryl cAMP which induces transformation from Pn3m to Ia3d lattice. The H-bonding interaction between the anionic phosphate group of cAMP and the glycerol backbone of the lipids has been evidenced by the increased frequency of the symmetric stretching vibration of PO2 group by 4-6 cm-l and broadening by 7 cm-l of the stretching vibration of glycerol C-OH group. It was found that dibutyryl cAMP interacts with the cubic phase through the pyrimidine ring and contrary to cAMP shows tendency to increase the number of gauche defects and to lower the mobility of the acyl chains.= 970 Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors

Polycythaemia-inducing mutations in the erythropoietin receptor (EPOR): mechanism and function as elucidated by epidermal growth factor receptor-EPOR chimeras

“…The proteasome complex prevents the renewal of surface EPOR by inhibiting the insertion of newly‐synthesized EPOR into the cell membrane (Verdier et al , ). The main signal for proteasomal degradation is lysine‐related ubiquitination.…”

Erythropoietin fosters both intrinsic and extrinsic neuronal protection through modulation of microglia, Akt1, Bad, and caspase‐mediated pathways

“…Several factors may determine both the concentration and temporal parameters that regulate the neuroprotective ability of EPO. During chronic administration, EPO can result in the formation of anti EPO antibodies (Casadevall et al ., 2002) and decrease the expression of the EPOR on the cell surface (Verdier et al ., 2000). As a result, biological function of EPO can be blocked at any concentration level.…”

Role of Ubiquitylation in Cellular Membrane Transport

“…For example, the erythropoietin receptor (EpoR) and its downstream signaling molecules, or the interleukin (IL)-2 and IL-9 receptors, were shown to be regulated by the proteasome (478). Although the rate of EpoR internalization is not affected, receptor recycling is enhanced in the presence of proteasome inhibitors, suggesting the proteasome is involved in EpoR sorting (441). Moreover, downstream effectors of EpoR and other cytokine receptors are regulated by ubiquitylation as well.…”