內質網(Endoplasmic Reticulum, ER)是由一系列圍繞在細胞膜及細胞核之間的雙層膜組成。內質網依其膜上附著之核糖體有無，可分為粗內質網(rough ER)及平滑內質網(smooth ER)。粗內質網因其核糖體，故有合成蛋白質的功能;平滑內質網則有製造脂質的作用。內質網是一個控制蛋白質合成、摺疊、成熟很重要的胞器，倘若內質網的恆定被改變，則會造成不完全摺疊的蛋白質累積在內質網，產生內質網壓力(Endoplasmic Reticulum Stress)，而對細胞的存活產生威脅。為了抵抗內質網壓力，細胞會啟動一連串反應期能紓解內質網壓力，這連串的反應稱做不完全摺疊蛋白反應(unfolded protein response, UPR)。除了UPR外，細胞也會啟動其它促生存的機制來反制內質網壓力。例如內質網壓力藉由釋放出內質網的鈣離子，促使細胞活化轉錄因子NF-κB的訊息傳遞，這就是著名的EOR (ER-overload response)。在這裡，我們發現，內質網壓力會使另一個已知有促生存功能的轉錄因子STAT3表現型式改變；此外，我們發現STAT3在內質網壓力下會與GRP78結合。內質網壓力下，僅管STAT3沒有傳統上代表活化的Tyr 705磷酸化現象，但STAT3在壓力下會入核；且出人意外的是，此時的STAT3在Ser 727的位置會遭到磷酸化。,這些都暗示著STAT3或許在壓力下扮演重要的角色,且值得我們深入探討。

　　From the perspective of protein biosynthesis, the endoplasmic reticulum (ER) can be viewed as a processing plant for folding and posttranslational modification of secreted and integral membrane proteins. Proteins are translocated into the ER in an unfolded state, it is the primary function of this organelle to modify and fold the translocated proteins to acquire their biologically active conformation. An imbalance between the load of client proteins facing the ER and the organelle’s ability to process that load is defined as ER stress. To cope with the stress, cells activate intracellular signaling pathway-the unfolded protein response (UPR), to provide adaptive responses for survival. In view of the fact that signal transducers and activators of transcription 3(STAT3) is constitutively activated in a wide variety of cancer cells and primary tumors, providing a growth advantage by inducing cell proliferation and inhibiting apoptosis, we sought to explore whether STAT3 was involved in the cellular response to ER stress. According to our data, we found that STAT3 exhibited a phenomenon under ER stress. While itsαform increases steadily, there’s a remarkable vanishment of STAT3β. Intriguingly, STAT3 translocates to the nuclear despite lacking any signs of Tyrosine 705 phosphorylation. Instead, it is phosphorylated at Serine 727. Interestingly, we found that STAT3 interacts with grp78, an ER stress-induced protein, suggesting that this interaction may lead to the translocation of STAT3.Our findings may provide a linkage for ER stress and STAT3 mediated signaling pathway, and its role under ER stress should be further studied.

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