FAF1最早被報導可以和Fas receptor結合並促進Fas ligand誘導的細胞凋亡路徑，往後的研究文獻說明FAF1蛋白會調控許多的生理功能，包含了發育、神經細胞的存活與細胞的癌化，其中有不少的研究顯示FAF1蛋白扮演抑癌蛋白的角色透過調控細胞凋亡、NF-κB路徑與泛素化蛋白的穩定度。我們利用了yeast two-hybrid screen的方法找到了FAF1的結合蛋白Ubiquitin與Ubc9。這樣的發現也與近期的報導有一致性。我們進一步在人類纖維肉瘤細胞建立穩定表現FAF1的細胞株，並且如預期的發現FAF1確實會促進Fas ligand誘導的caspase活化與細胞凋亡，以及結合泛素化蛋白的功能。有趣的是我們利用免疫螢光染色技術發現大量表現FAF1蛋白和內生性的FAF1蛋白主要會座落於細胞核內，而細胞質則呈現較弱的訊號。此外，我們也發現FAF1與Gal4-DBD的融合蛋白會抑制Gal4-responsive reporter的轉錄活性，而NF-κB的轉錄活性也會受到FAF1的抑制。這些的結果推測FAF1促進Fas ligand誘導的細胞凋亡也許是透過調控細胞核內的基因轉錄，而這些基因涉及在Fas誘導的細胞凋亡與NF-κB存活路徑之中。

Fas-associated factor 1 (FAF1) was originally identified as a interacting partner of Fas receptor that enhances apoptosis initiated through Fas antigen. Further studies have revealed that FAF1 functions in diverse biological processes, including normal development, neuronal cell survival and tumorigenesis. In particular, there are compelling evidences implicating FAF1 as a tumor suppressor involved in the modulation of apoptosis and NF-κB signaling, as well as in ubiquitin-mediated protein turnover. Using the yeast two-hybrid screen, we have isolated the ubiquitin and ubiquitin-conjugating enzyme Ubc9 as FAF1-interacting proteins. This finding is in agreement with the recently published data. We further established human fibrosarcoma HT1080 cell lines that exhibited stable expression of ectopic FAF1. Consistently, we demonstrated that ectopic expression of FAF1 enhances Fas-induced caspase activation and apoptosis, and binds to ubiquitinated substrates in vivo. Interestingly, we found that both ectopic and endogenous FAF1 was mainly localized to the nucleus with a faint cytoplasmic staining by immunofluorescence analysis. Moreover, we found that fusion of FAF1 to Gal4-DBD results in repression of transcription from Gal4-responsive reporter plasmids. Also, FAF1 can suppress NF-κB transcriptional activity. These findings suggest that FAF1 promotes sensitivity to Fas from a nuclear location, probably by regulating the transcription of genes involved in Fas-induced apoptosis and/or NF-κB survival pathway.

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