Regulation of inhibitor of apoptosis proteins after traumatic brain injury

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Physiology and Biophysics

First Committee Member

Robert W. Keane - Committee Chair


The 'inhibitor of apoptosis' (IAP) gene family encodes a group of structurally related proteins that suppress apoptotic cell death and are involved in signaling cascades and protein modifications. The expression and subcellular distribution of IAP family members, cIAP-1, cIAP-2 and XIAP were analyzed in the normal rat brain and in brains subjected to moderate traumatic brain injury (TBI). All IAPs were expressed in neurons in the cortex and hippocampus, but their regional and subcellular distribution differed. TBI transiently increased cIAP-1 and cIAP-2 expression, but transiently decreased XIAP expression. TBI increased binding of TRAF1 to cIAP-2 but not to cIAP-1, and resulted in polyubiquitination of TRAF2. Immunoprecipitation and immunoblots of brain extracts demonstrated that levels of monoubiquitinated XIAP increase after TBI, but with a different time course in cortex and hippocampus. Similar alterations in IAP expression, association with signaling intermediates and protein modifications following TBI were observed in cortex both ipsi- and contra-lateral to the injury. These results demonstrate that IAPs govern diverse cellular interactions following TBI.


Biology, Molecular; Biology, Neuroscience; Health Sciences, Pathology

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