tailieunhanh - Báo cáo khoa học: Human mitochondrial transcription factor A possesses multiple subcellular targeting signals

The mitochondrial transcription factor A (TFAM) is a member of a high-mobility group (HMG) family represented mostly by nuclear proteins. Although nuclear localization of TFAM has been demonstrated in some tumors and after treatment of tumor cells with anticancer drugs, the signifi-cance of these observations has not been fully elucidated. | ễFEBS Journal Human mitochondrial transcription factor A possesses multiple subcellular targeting signals Viktoriya Pastukh1 Inna Shokolenko1 Bin Wang2 Glenn Wilson1 and Mikhail Alexeyev1 3 1 Department of Cell Biology and Neuroscience University of South Alabama Mobile AL USA 2 Department of Mathematics and Statistics University of South Alabama Mobile AL USA 3 Institute of Molecular Biology and Genetics Kyiv Ukraine Keywords chemotherapy cisplatin etoposide mitochondrialtranscription factor A nuclear localization sequence Correspondence M. Alexeyev Department of Cell Biology and Neuroscience University of South Alabama 307 University Blvd. MSB1201 Mobile AL 36688 USA Fax 1 251 460 6771 Tel 1 251 460 6789 E-mail malexeye@ Received 29 July 2007 revised 12 October 2007 accepted 25 October 2007 doi The mitochondrial transcription factor A TFAM is a member of a high-mobility group HMG family represented mostly by nuclear proteins. Although nuclear localization of TFAM has been demonstrated in some tumors and after treatment of tumor cells with anticancer drugs the significance of these observations has not been fully elucidated. Here we report that both TFAM overexpression and impairment of its mitochondrial targeting can result in nuclear accumulation of the protein. Both M1 and M7 methionines of human TFAM hTFAM can be used for translation initiation with almost equal efficiency resulting in two polypeptides. The shorter polypeptide however is not located in the nucleus despite truncation in the mitochondrial targeting sequence and both isoforms are targeted to mitochondria with similar efficiency. We further demonstrate that nuclear TFAM confers significant cytoprotection against the chemotherapeutic drugs etoposide camptothecin and cisplatin. Three regions of hTFAM HMG-like domain 1 HMG1 and HMG-like domain 2 HMG2 as well as the tail region can effect nuclear accumulation of enhanced green fluorescent protein .