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Cancer Res 2007, PMID: 17942934

Deficiency of NRH:quinone oxidoreductase 2 differentially regulates TNF signaling in keratinocytes: up-regulation of apoptosis correlates with down-regulation of cell survival kinases.

Ahn, Kwang Seok; Gong, Xing; Sethi, Gautam; Chaturvedi, Madan M; Jaiswal, Anil K; Aggarwal, Bharat B

NRH:quinone oxidoreductase 2 (NQO2) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinones and quinoid compounds to hydroquinones. Although the role of a homologue, NAD(P)H:quinone oxidoreductase 1 (NQO1), is well defined in oxidative stress, neoplasia, and carcinogenesis, little is known about the mechanism of actions of NQO2 in these cellular responses. Whether NQO2 has any role in tumor necrosis factor (TNF) signaling was investigated using keratinocytes derived from wild-type and NQO2 knockout (NQO2-/-) mice. Although exposure of wild-type cells to TNF led to activation of nuclear factor-kappaB (NF-kappaB) and IkappaBalpha kinase, IkappaBalpha degradation, p65 phosphorylation, and p65 nuclear translocation, this cytokine had no effect on NQO2-/- cells. Deletion of NQO2 also abolished TNF-induced c-Jun NH2-terminal kinase, Akt, p38, and p44/p42 mitogen-activated protein kinase activation. The induction of various antiapoptotic gene products (MMP-9, cyclin D1, COX-2, IAP1, IAP2, Bcl-2, cFLIP, and XIAP) by TNF was also abolished in NQO2-/- cells. This correlated with potentiation of TNF-induced apoptosis as indicated by cell viability, Annexin V staining, and caspase activation. In agreement with this, we also found that TNF activated NQO2, and NQO2-specific small interfering RNA abrogated the TNF-induced NQO2 activity and NF-kappaB activation. Overall, our results indicate that deletion of NQO2 plays a differential role in TNF signaling pathway: by suppressing cell survival signals and potentiating TNF-induced apoptosis.

Diseases/Pathways annotated by Medline MESH: Skin Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

p38 → TNF: " Deletion of NQO2 also abolished TNF induced c-Jun NH2-terminal kinase, Akt, p38 , and p44/p42 mitogen activated protein kinase activation "

p44/p42 → TNF: " Deletion of NQO2 also abolished TNF induced c-Jun NH2-terminal kinase, Akt, p38, and p44/p42 mitogen activated protein kinase activation "

p44/p42 → TNF: " Deletion of NQO2 also abolished TNF induced c-Jun NH2-terminal kinase, Akt, p38, and p44/p42 mitogen activated protein kinase activation "

Akt → TNF: " Deletion of NQO2 also abolished TNF induced c-Jun NH2-terminal kinase, Akt , p38, and p44/p42 mitogen activated protein kinase activation "

cyclin D1 → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1 , COX-2, IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

IAP1 → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2, IAP1 , IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

cFLIP → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2, IAP1, IAP2, Bcl-2, cFLIP , and XIAP ) by TNF was also abolished in NQO2-/- cells "

COX-2 → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2 , IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

XIAP → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2, IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

MMP-9 → TNF: " The induction of various antiapoptotic gene products ( MMP-9 , cyclin D1, COX-2, IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

cyclin → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2, IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

COX-2 → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2 , IAP1, IAP2, Bcl-2, cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

Bcl-2 → TNF: " The induction of various antiapoptotic gene products ( MMP-9, cyclin D1, COX-2, IAP1, IAP2, Bcl-2 , cFLIP, and XIAP ) by TNF was also abolished in NQO2-/- cells "

NF-kappaB → TNF: " In agreement with this, we also found that TNF activated NQO2, and NQO2-specific small interfering RNA abrogated the TNF induced NQO2 activity and NF-kappaB activation "

NQO2 → TNF: " In agreement with this, we also found that TNF activated NQO2 , and NQO2-specific small interfering RNA abrogated the TNF induced NQO2 activity and NF-kappaB activation "

Manually curated Databases

No curated data.