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dc.creatorVaradarajan, Shankar
dc.date.accessioned2012-09-07T16:45:18Z
dc.date.available2012-09-07T16:45:18Z
dc.date.created2008-08
dc.date.issued2012-09-07
dc.identifier.urihttp://hdl.handle.net/2152/17812
dc.descriptiontext
dc.description.abstractp38 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.en_US
dc.format.mediumelectronic
dc.language.isoengen_US
dc.rightsCopyright 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.lcshProtein kinases
dc.subject.lcshMitogens
dc.subject.lcshCell death
dc.subject.lcshAutophagic vacuoles
dc.subject.lcshProstate--Cancer--Treatment
dc.titleP38 MAPKs coordinately regulate distinct phases of autophagy and lysomal biogenesisen_US
dc.description.departmentCellular and Molecular Biologyen_US
thesis.degree.departmentCellular and Molecular Biologyen_US
thesis.degree.disciplineCell and Molecular Biologyen_US
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US


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