The peptidyl-prolyl isomerase Pin1 regulates the stability of granulocyte-macrophage colony-stimulating factor mRNA in activated eosinophils.
The infiltration, accumulation and degranulation of eosinophils in the lung represents a hallmark of active asthma. In vivo or in vitro eosinophil activation triggers the secretion of the antiapoptotic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We now identify Pin1, a cis-trans isomerase, as an essential component of the ribonucleoprotein complex responsible for GM-CSF mRNA stabilization, cytokine secretion and the survival of activated eosinophils. Pin1 regulated the association of the AU-rich element-binding proteins AUF1 and hnRNP C with GM-CSF mRNA, accelerating or slowing decay, respectively. These data indicate Pin1 is a key mediator of GM-CSF production.
Shen
Zhong-Jian
ZJ
The Waisman Center for Developmental Disabilities, the Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine, Madison, Wisconsin 53705, USA.
Esnault
Stephane
S
Malter
James S
JS
D000485:Allergens / Q000276:immunology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004804:Eosinophils / Q000201:enzymology* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
D000485:Allergens; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006820:Hyaluronic Acid; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase