title: Pro-apoptotic action of PAR-4 involves inhibition of NF-kappaB activity and suppression of BCL-2 expression.
abstract: Par-4(1) (prostate apoptosis response 4) is known to function at an early stage in apoptosis in several different cell types, including neurons. On the other hand, activation of the transcription factor NF-kappaB can prevent apoptosis in various cancer cells and neurons. We now report that overexpression of full-length Par-4 in cultured PC12 cells results in a suppression of basal NF-kappaB DNA-binding activity and NF-kappaB activation following trophic factor withdrawal (TFW). The decreased NF-kappaB activity is correlated with enhanced apoptosis. Conversely, NF-kappaB activity is increased and vulnerability to apoptosis reduced in cells overexpressing a dominant-negative form of Par-4. Par-4 overexpression or functional blockade had no effect on AP-1 DNA-binding activity. Expression of the antiapoptotic protein Bcl-2 was dramatically reduced in PC12 cells overexpressing Par-4. Our data suggest that suppression of NF-kappaB activation plays a major role in the proapoptotic function of Par-4.
authors.affiliation: Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA.
authors.forename: S
authors.initials: S
authors.lastname: Camandola
authors.forename: M P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C090468:TP53BP2 protein, human; C101296:prostate apoptosis response-4 protein