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Abstract:
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p38 mitogen -activated protein kinases (MAPKs ) control the endocytic trafficking of various growth -related cell surface receptors and transporters . Herein , I demonstrate that p38 MAPKs also regulate autophagy , or the process of self -cannibalism . In my studies , inhibition of p38 MAPKs triggered rapid formation of autophagosomes in prostate cancer cells , even under nutrient -rich conditions , and remarkably , the autophagosomal membranes emanated from endoplasmic reticulum exit sites via the concerted actions of the small GTPases , ARF1 and SAR1 . Once formed , the autophagosomes fused with late endosomes and /or lysosomes , in a Rab7 -dependent manner , to form “hybrid organelles” that were co -labeled with ER , autophagic , late endosomal , and lysosomal markers . Unlike other inducers of autophagy , however , inhibition of p38 MAPKs suppressed the fission of hybrid organelles , resulting in a profound but reversible accumulation of large cytoplasmic vacuoles . Thus , in addition to their previously reported roles in endocytosis , p38 MAPKs appear to coordinately regulate autophagy and the downstream biogenesis and fission of hybrid organelles . |