St. Jude Children’s Research Hospital,、Loyoba大學和京都大學的研究人員發(fā)現(xiàn)用來調節(jié)新蛋白折疊的部分分子機制還包含一種遺傳性反應,，這個反應能夠擴大蛋白質折疊和包裝的工廠（內質網(wǎng)）,。研究人員將這些發(fā)現(xiàn)公布在2004年10月15日的Journal of Cell Biology（JCB）上,。
蛋白質折疊工廠（內質網(wǎng)）的構建之間的這種關連能夠確保這兩個過程在細胞需要快速制造,、折疊和分泌大量特定蛋白時能協(xié)調運作,。
研究人員發(fā)現(xiàn)細胞會產生一種叫做XBP1的分子以滿足蛋白質折疊機器不斷增長的需要,。這種對折疊蛋白需求的增長會導致所謂的未折疊蛋白反應（UPR）以及蛋白質折疊和包裝的工廠的膨脹,。UPR還能促進細胞產生分子伴侶,。
XBP1能夠引發(fā)細胞產生卵磷脂。卵磷脂是構成內質網(wǎng)（ER）的重要建筑材料,。ER中的膜能充當包裝已折疊蛋白的包膜,。當離開ER后,，這個包膜就會融合到細胞膜內側。一旦融入細胞膜,，包膜就會打開并將其內的蛋白質放出細胞外,。
通過將分子伴侶的制造和卵磷脂的合成聯(lián)系起來，XBP1能夠協(xié)調新ER的構建和裝備并以此提高細胞折疊和運送蛋白的能力,。
研究人員通過對是小鼠的纖維原細胞的研究發(fā)現(xiàn)了這個機制,。他們將XBP1基因插入一種病毒并利用這種轉基因病毒將這種基因引入纖維原細胞內。XBP1基因使纖維原細胞膜產生有關的關鍵酶類的活性明顯增加,。因為,，已經知道UPR能夠活化XBP1基因，所以這項研究表明XBP1能夠將ER的膨脹和增加折疊和包裝分泌性蛋白的能力聯(lián)系在一起,。
這項研究解釋了細胞能夠快速滿足增加特定蛋白產量需求的原因,，即通過折疊和裝配蛋白任務的協(xié)同來達成這種任務。而且,，這些發(fā)現(xiàn)也促進了人們對細胞生物學的進一步了解,。
相關文章：
EDEM Contributes to Maintenance of Protein Folding Efficiency and Secretory Capacity.J. Biol. Chem., Vol. 279, Issue 43, 44600-44605, October 22, 2004 PDF(500K)
Hampton, R. Y. 2002. ER-associated degradation in protein quality control and cellular regulation. Current Opinions in Cell Biology 14:476-482. PDF (188K)
Cronin, S. R., Rao, R., Hampton, R. Y. 2002. Cod1p/Spf1p is a P-type ATPase involved in ER function and CA2+ homeostasis. Journal of Cell Biology 157:1017-1028. PDF (476K)
Gardner RG, Shearer AG, Hampton RY. 2001. In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Molecular Cell Biology 21:4276-91. PDF (840K)
Gardner, R., Shan, H., Matsuda, S., and R. Hampton. 2001. An oxysterol-derived positive signal for 3-hydroxy-3-methylglutaryl-CoA reductase degradation in yeast. Journal of Biological Chemistry 276: 8681-8684. PDF (652K)
Bays, N., Gardner, R., Seelig, L., Joazeiro, C., and R. Hampton. 2001. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nature Cell Biology 3:24-29. PDF (355K)
Gardner, R., Swarbrick, G., Bays, N., Cronin, S., Wilhovsky, S., Seelig, L., Kim, C., and R. Hampton. 2000. Endoplasmic reticulum degradation requires lumen to cytosol signaling: transmembrane control of Hrd1p by Hrd3p. Journal of Cell Biology 151:69-82. Full Text PDF (688K)
Wilhovsky, S., Gardner, R., and R. Hampton. 2000. HRD gene dependence of endoplasmic reticulum degradation. Molecular Biology of the Cell 11:1697-1708. Full Text PDF (428K)
R. Hampton. 2000. ER stress response: getting the UPR hand on misfolded proteins. Current Biology 10:R518-521. Full Text
R. Hampton. 2000. Cholesterol homeostasis: ESCAPe from the ER. Current Biology 10:R298-301. Full Text PDF
Cronin, S., Khoury, A., Ferry, D., and R. Hampton. 2000. Regulation of HMG-CoA reductase degradation requires the P-type ATPase Cod1p/Spf1p. Journal of Cell Biology 148:915-924. Full Text PDF (324K)
Gardner, R. and R. Hampton. 1999. A 'distributed degron' allows regulated entry into the ER degradation pathway. Embo 18:5994-6004. Full Text PDF (332K)
Gardner, R. and R. Hampton. 1999. A highly conserved signal controls degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in eukaryotes. Journal of Biological Chemistry 274:31671-31678. Full Text PDF (353K)
Gardner, R., Cronin, S., Leder, B., Rine, J., and R. Hampton. 1998. Sequence determinants for regulated degradation of yeast 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Molecular Biology of the Cell 9:2611-2626. Full Text PDF (553K)
