tailieunhanh - Báo cáo khoa hoc : Bimodal targeting of cytochrome P450s to endoplasmic reticulum and mitochondria: the concept of chimeric signals

Targeting signals are critical for proteins to find their specific cellular desti-nation. Signals for protein targeting to the endoplasmic reticulum (ER), mitochondria, peroxisome and nucleus are distinct and the mechanisms of protein translocation across these membrane compartments also vary markedly. | fFEBS Journal MINIREVIEW Bimodal targeting of cytochrome P450S to endoplasmic reticulum and mitochondria the concept of chimeric signals Narayan G. Avadhani Michelle C Sangar Seema Bansal and Prachi Bajpai Department of AnimalBiology and the Mari Lowe Center for Comparative Oncology Schoolof Veterinary Medicine University of Pennsylvania Philadelphia PA USA Keywords chimeric signals cytochrome P450 mitochondrial targeting multiple subcellular localization protease processing protein phosphorylation Correspondence N. G. Avadhani Department of Animal Biology and the Mari Lowe Center for Comparative Oncology Schoolof Veterinary Medicine University of Pennsylvania Philadelphia PA 19104 USA Fax 1 215 573 6810 Tel 1 215 898 8819 E-mail narayan@ Received 18 May 2011 revised 19 July 2011 accepted 31 August 2011 doi Targeting signals are critical for proteins to find their specific cellular destination. Signals for protein targeting to the endoplasmic reticulum ER mitochondria peroxisome and nucleus are distinct and the mechanisms of protein translocation across these membrane compartments also vary markedly. Recently however a number of proteins have been shown to be present in multiple cellular sites such as mitochondria and ER cytosol and mitochondria plasma membrane and mitochondria and peroxisome and mitochondria suggesting the occurrence of multimodal targeting signals in some cases. Cytochrome P450 monooxygenases CYPs which play crucial roles in pharmacokinetics and pharmacodynamics of drugs and toxins are the prototype of bimodally targeted proteins. Several members of family 1 2 and 3 CYPs have now been reported to be associated with mitochondria and plasma membrane in addition to the ER. This review highlights the mechanisms of bimodal targeting of CYP1A1 2B1 2E1 and 2D6 to mitochondria and ER. The bimodal targeting of these proteins is driven by their N-terminal signals which carry essential elements of both ER .