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http://purl.uniprot.org/citations/11564864http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11564864http://www.w3.org/2000/01/rdf-schema#comment"Benzo[a]pyrene [B(a)P], a potent procarcinogen found in combustion products such as diesel exhaust and cigarette smoke, has been recently shown to activate the c-Jun NH(2)-terminal kinase 1 (JNK1) and induce caspase-3-mediated apoptosis in Hepa1c1c7 cells. However, the molecules of the signaling pathway that control the mitogen-activated protein kinase cascades induced by B(a)P and the interaction between those and apoptosis by B(a)P have not been well defined. We report here that B(a)P promoted Cdc42/Rac1, p21-activated kinase 1 (PAK1), and JNK1 activities in 293T and HeLa cells. Moreover, alpha-PAK-interacting exchange factor (alpha PIX) mRNA and its protein expression were upregulated by B(a)P. While overexpression of an active mutant of alpha PIX (DeltaCH) facilitated B(a)P-induced activation of Cdc42/Rac1, PAK1, and JNK1, overexpression of mutated alphaPIX (L383R, L384S), which lacks guanine nucleotide exchange factor activity, SH3 domain-deleted alphaPIX (Delta SH3), which lacks the ability to bind PAK, kinase-negative PAK1 (K299R), and kinase-negative SEK1 (K220A, K224L) inhibited B(a)P-triggered JNK1 activation. Interestingly, overexpression of alphaPIX (Delta CH) and a catalytically active mutant PAK1 (T423E) accelerated B(a)P-induced apoptosis in HeLa cells, whereas alphaPIX (Delta SH3), PAK1 (K299R), and SEK 1 (K220A, K224L) inhibited B(a)P-initiated apoptosis. Finally, a preferential caspase inhibitor, Z-Asp-CH2-DCB, strongly blocked the alphaPIX (Delta CH)-enhanced apoptosis in cells treated with B(a)P but did not block PAK1/JNK1 activation. Taken together, these results indicate that alphaPIX plays a crucial role in B(a)P-induced apoptosis through activation of the JNK1 pathway kinases."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.org/dc/terms/identifier"doi:10.1128/mcb.21.20.6796-6807.2001"xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Arai H."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Kataoka H."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Tanaka M."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Yoshii S."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Sugimura H."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Otsuki Y."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Hanai H."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/author"Fujiyama T."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/name"Mol Cell Biol"xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/pages"6796-6807"xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/title"Involvement of alpha-PAK-interacting exchange factor in the PAK1-c-Jun NH(2)-terminal kinase 1 activation and apoptosis induced by benzo[a]pyrene."xsd:string
http://purl.uniprot.org/citations/11564864http://purl.uniprot.org/core/volume"21"xsd:string
http://purl.uniprot.org/citations/11564864http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11564864
http://purl.uniprot.org/citations/11564864http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11564864
http://purl.uniprot.org/uniprot/Q15052#attribution-18CF7289D7177BEBCFF5AE76AC7AFE73http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/11564864