FOXO (single Forkhead Box O) 轉(zhuǎn)錄因子已成為細(xì)胞功能調(diào)控因子的一個(gè)主要匯聚點(diǎn),，包括“胰島素/IGF1信號(hào)作用(IIS)通道”,。IIS參與各種不同的生物過(guò)程,，包括壽命的調(diào)控,。在線蟲(chóng)中，F(xiàn)OXO轉(zhuǎn)錄因子DAF-16a在IIS通道中扮演一個(gè)主要角色,。DAF-16a是兩個(gè)同形物中的一個(gè),，調(diào)控線蟲(chóng)的壽命、應(yīng)激反應(yīng)和“多爾滯育”(dauer diapause),，但尚不清楚DAF-16在調(diào)控這些不同生物過(guò)程中是怎樣實(shí)現(xiàn)其特異性的,。
現(xiàn)在，一個(gè)新的DAF-16同形物,，即DAF-16d/f,，已被識(shí)別出來(lái)，它在壽命調(diào)控中也很重要,。一系列涉及基因表達(dá)操縱的實(shí)驗(yàn)表明,，各種不同DAF-16同形物之間的組合互動(dòng)的作用是，在整個(gè)生物的背景下微調(diào)由IIS調(diào)控的過(guò)程,。線蟲(chóng)似乎是利用來(lái)自一個(gè)基因的多種同形物來(lái)微調(diào)由IIS調(diào)控的過(guò)程的,，這與哺乳動(dòng)物中的情況形成對(duì)比——在哺乳動(dòng)物中，四個(gè)不同的FOXO基因執(zhí)行重疊的和截然不同的功能,。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature09184
A new DAF-16 isoform regulates longevity
Eun-Soo Kwon,Sri Devi Narasimhan,Kelvin Yen& Heidi A. Tissenbaum
The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity1, 2, 3, 4, 5. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway2, 3, 6, 7. One of two isoforms4, 5, 8, DAF-16a, is known to regulate longevity, stress response and dauer diapause8, 9, 10, 11. However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate IIS-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases, and regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions6, 12, and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the IIS-mediated processes in the context of a whole organism.
