Ducut Sigala Jeanette L, Bottero Virginie, Young David B, Shevchenko Andrej, Mercurio Frank, Verma Inder M
Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2004 Jun 25;304(5679):1963-7. doi: 10.1126/science.1098387.
The nuclear factor-kappa B (NF-kappaB) family of transcription factors plays a seminal role in inflammation, apoptosis, development, and cancer. Modulation of NF-kappaB-mediated gene expression in response to diverse signals is coordinated by the IkappaB kinase (IKK) complex. We identified ELKS, an essential regulatory subunit of the IKK complex. Silencing ELKS expression by RNA interference blocked induced expression of NF-kappaB target genes, including the NF-kappaB inhibitor IkappaBalpha and proinflammatory genes such as cyclo-oxygenase 2 and interleukin 8. These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IkappaBalpha to the IKK complex and thus serves a regulatory function for IKK activation.
核因子-κB（NF-κB）转录因子家族在炎症、细胞凋亡、发育和癌症中起着关键作用。IκB激酶（IKK）复合物可协调对多种信号作出反应的NF-κB介导的基因表达的调节。我们鉴定出ELKS是IKK复合物的一个必需调节亚基。通过RNA干扰使ELKS表达沉默可阻断NF-κB靶基因的诱导表达，包括NF-κB抑制剂IκBα以及诸如环氧化酶2和白细胞介素8等促炎基因。这些细胞在对细胞因子作出反应时也无法免受细胞凋亡的影响。ELKS可能通过将IκBα募集到IKK复合物发挥作用，从而对IKK激活起到调节功能。
