Show simple item record

dc.contributor.advisorBratton, Shawn B.en
dc.creatorVaradarajan, Shankaren
dc.date.accessioned2012-09-07T16:45:18Zen
dc.date.available2012-09-07T16:45:18Zen
dc.date.created2008-08en
dc.date.issued2012-09-07en
dc.identifier.urihttp://hdl.handle.net/2152/17812en
dc.descriptiontexten
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
dc.format.mediumelectronicen
dc.language.isoengen
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.en
dc.subject.lcshProtein kinasesen
dc.subject.lcshMitogensen
dc.subject.lcshCell deathen
dc.subject.lcshAutophagic vacuolesen
dc.subject.lcshProstate--Cancer--Treatmenten
dc.titleP38 MAPKs coordinately regulate distinct phases of autophagy and lysomal biogenesisen
dc.description.departmentCellular and Molecular Biologyen
thesis.degree.departmentCellular and Molecular Biologyen
thesis.degree.disciplineCell and Molecular Biologyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record