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Title: Molecular function and regulation of the Bax-associating protein MOAP-1
Keywords: Apoptosis, mitochondria, Bcl-2 family, MOAP-1, ubiquitin, proteasome
Issue Date: 12-Sep-2007
Citation: FU NAIYANG (2007-09-12). Molecular function and regulation of the Bax-associating protein MOAP-1. ScholarBank@NUS Repository.
Abstract: Bax is a central regulator for controlling the release of apoptogenic factors from mitochondria. MOAP-1 has previously been identified as a Bax-associating protein, but its regulation and functional relationship with Bax in apoptosis signalling remains unclear. In this thesis, MOAP-1 is found to be a short-lived mitochondrial protein due to constitutive degradation by the ubiquitin-proteasome system. MOAP-1 is rapidly up-regulated by multiple apoptotic stimuli through inhibition of its poly-ubiquitination process. Elevation of MOAP-1 levels sensitizes cells to apoptotic stimuli, whereas, cells with stable expression of MOAP-1 siRNAs are resistant to multiple apoptotic stimuli. Remarkably, the effect of recombinant Bax and tBid proteins in stimulating release of cytochrome c from isolated mitochondria is significantly compromised by the depletion of MOAP-1. Identification of MOAP-1 as a mitochondrial effector of Bax and a substrate of the ubiquitin-proteasome pathway would have an important implication for conceptualizing novel therapeutic strategies in combating human diseases.
Appears in Collections:Ph.D Theses (Open)

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