P38 MAPKs coordinately regulate distinct phases of autophagy and lysomal biogenesis


P38 MAPKs coordinately regulate distinct phases of autophagy and lysomal biogenesis

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dc.contributor.advisor Bratton, Shawn B.
dc.creator Varadarajan, Shankar
dc.date.accessioned 2012-09-07T16:45:18Z
dc.date.available 2012-09-07T16:45:18Z
dc.date.created 2008-08
dc.date.issued 2012-09-07
dc.identifier.uri http://hdl.handle.net/2152/17812
dc.description.abstract 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.
dc.format.medium electronic
dc.language.iso eng
dc.rights Copyright © is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.
dc.subject.lcsh Protein kinases
dc.subject.lcsh Mitogens
dc.subject.lcsh Cell death
dc.subject.lcsh Autophagic vacuoles
dc.subject.lcsh Prostate--Cancer--Treatment
dc.title P38 MAPKs coordinately regulate distinct phases of autophagy and lysomal biogenesis
dc.description.department Cellular and Molecular Biology
dc.type.genre Thesis
dc.type.material text
thesis.degree.department Cellular and Molecular Biology
thesis.degree.discipline Cell and Molecular Biology
thesis.degree.grantor The University of Texas at Austin
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy

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