Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration (Nature Cell Biology, 7:837-843, August 2005)

報告日期: 2005/10/25
報告時間: 15:10/16:00
報告學生: 高遠忠
講評老師: 呂增宏
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Prohibitin is required for Ras-induced Raf–MEK–ERK activation and epithelial cell migration

 

Nature cell biology, 2005

 

Speaker:高遠忠

Commentator:呂增宏 老師

Time:2005/10/25 15:10~14:00

 

Prohibitin (PHB) is an evolutionarily conserved protein that is involved in diverse cellular processes such as proliferation and energy metabolism. In previously study, the authors found that HeLa cells transfected with siRNAs (siPHB) to suppress PHB expression was a profound alteration in their morphology. In this paper, they performed SEM, TEM and confocal microscope to observe that knockdown PHB in HeLa cells induced the aggregation and reduced migration ability. In addition to morphology change, the cells transfected with siPHB grew mutilelayer, had no intercellular space and lack membrane protrusions. On the other hand, Ras protein is the major controller of the signaling pathway responsible for normal growth and malignant transformation. Ras induced epithelial cell migration through Raf-MEK-ERK signaling pathway. The authors demonstrated that PHB involved in Ras-Raf-MEK-ERK pathway and is essential required for Raf activation. Recently, PHB has reported to be a target used by bacterial pathogen to modulate MAPK cascade, leading to IL-8 secretion. Furthermore, PHB has been shown to be overexpressed in carcinomas and neoplastic thyroid cancer. And activating Ras mutations are found in more than 20% of all tumors, suggest that PHB might be a possible target for tumor therapy.

 

References

1. Prohibitin: potential role in senescence, development, and tumor suppression. Exp. Gerontol. 30, 99–124 (1995).

2.  Protein kinase A blocks Raf-1 activity by stimulating 14–3-3 binding and blocking Raf-1 interaction with Ras. J. Biol. Chem. 278, 29819–29823 (2003).