2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Chang, YZ

Duan, XL

Qian, ZM

Yu, P

PolyU Institutional Repository

???????????＊于　鹏1　常彦忠1 ,2　钱忠明1 ,2■(1 ???????????????????? ,??? 050016;2??????????????????????? ,????)??　铁转运刺激因子(stimulator of Fe transport , SFT)是近年新发现的一个重要的铁代谢蛋白 。SFT是一种跨膜糖蛋白 ,含 6个跨膜区域 ,在第一个细胞内环中含有功能上十分重要的 REIHE序列。它广泛分布于各组识 ,其主要功能是促进转铁蛋白结合铁和非转铁蛋白结合铁的转运 。SFT 的基因表达和功能发挥受铁的调控 。遗传性血色素沉着病人的肝脏内 SFT mRNA的表达显著增加 ,因而SFT 超表达可能与遗传性血色素沉着病的形成有关 。???　铁转运刺激因子;铁代谢;铁转运;遗传性血色素沉积症?????　Q51　　?????????????? ,???????????????? 。??????????-?????????????? ,?????????????????[ 1 , 2] 。1997? ,Gutierrez?[ 3]?????????????????? 1400bp? cDNA ,????????????????????? ,?????????????(stimulator ofFe transport , SFT)。???? ,SFT ????????????????????????? ,?????????????????? 。SFT ??????????????????????? ,???????????????????(?????)??? 。??????? SFT ???????? 、???? 、??????????????????????。? 、SFT????? 、?????SFT ????????????[ 3 ,4] ,?????? 、? 、????????????;??? 、?? 、?? 、??????????????? 。????????????[ 5] ,??? 、?? 、?? 、? 、? 、? 、???????? SFT mRNA?? 。Barisani?[ 6]?Yu?[ 7]???? ,?????SFT??????????????????? 。????????? ,SFT ???????????????(re-cycling endosomes)?。SFT ???????? ,???2.5%β-????? 1%SDS??????????????? ,??????? SFT ??????????? ATP ?? ,?? SFT ?? ABC(ATP-binding cassette)??????????? ,?? SFT??????? ABC ?? Walker ??。??Paulsen?(1997)???????????? CDF(cation diffusion facilitator)??? 13????? ,????? 6????? ,?? SFT ???????????? ,?????????? CDF ????????? 。SFT???? 338???????????????[ 7] ,?? 6?????(M1 ～ M6)。?? M1 、M3?M5?????????????? ,?????????? 。SFT ??????? , ??Glu149-Met224? His246-Leu296??????????? 。SFT ???????????(L4)??????????(L5)(? 1)。L2??????????????(sensor),??????? SFT ? L2?????? REIHE?????[ 3] ,?????????? Ftr1 ??????????????? ———REXXE???? 。?? Ftrl? REXXE ??? Glu※Ala????? Ftrl???????;?? ,??SFT ?REIHE???Glu?Ala ?? ,??????????????? 。Gutierrez?(1998)?? FISH??????SFT ???? 10????(10q21?)(? 2)。 SFT ? ? ? ? 5 ? ? ? GATA? , 2?TATA? , 1?SP1???? , 1?γ-???＊?????? 、???? UGC ???????????????■????·57·?????? 2004?? 35?? 1?????(IFN-γ)????? CTG/TG/TANNC/T ,??SFT ????????????????? 。SFT cDNA ? 1404bp , ???? ORF(open readingframe),?3' ????(Untranslated region ,UTR)???1???????? , 1???????? 1 ?41????? 。? 41????? 180?????XFGFR(Xenopus FGF receptor)????????????———TIE(translation inhibitory element)? 65.8%???? , 78%????? 。?????????TIE????????? 。?? , ?SFT5' ???? 1? Y ? ,??????? CCAAT ?? ,??????? DNA ? RNA?????????? 。PCR???? SFT 3' ????????1000???????????? ,???????SFT ??????? ,????????????????????????。? 1　SFT???????? 2　? SFT????????　　? 、SFT????????? SFT ??? HeLa??????????????????? ,???????????????[ 3 , 8] 。???????? 、??? A 、2 ,4-?????? K562??? ,???ATP ?????? 50%,Fe3+? Fe2+?????? ,??? K562??? SFT ??????????????[ 3] 。? 、? 、??????? SFT ????? ,??????????? K562 ??????????????????? , ????????? SFT ?????。SFT ?HeLa??[ 9]?????????????????????????。?????[ 9] ,SFT???????? Fe3+? Fe2+??????????。??????????????SFT??????????????。SFT ????????????????????? ,??????????????????????? 。SFT ??????????? ,??? SFT ??????????????????????????[ 3 ,8] 。????? ,???????????????????? 。?????????????????????????(transfer-rin receptor ,TfR)?? 。??????????。????????????? ,?????? pH ?? ,????????????? ,????????????????[ 1 ,2] 。????????? ,????????? DMT1(divalent metal transporter1)?????。SFT ????????????[ 3 ,8] ,??? SFT ????????????。SFT? DMT1 ???????????????? ,???????。? 、SFT???????SFT?????????????????(Gutierrez ?.1998)。???? BHK ??(Gutierrez?.1998)、HeLa??[ 4]??????????(des-ferrioxamine)? , SFT mRNA ??;BHK ?? 、HepG2??[ 3]???????? , SFT mRNA ?????????????????? ,??????????。SFT ?????????????????????????。??????[ 3] , PMA(phorbol12-myristate 13-acetate)??? K562??? SFT mR-NA??? ,??SFT mRNA? 5'? 3'? UTR? ,??????????? ,??? SFT ????????????????。?? SFT-ORF cRNA???????????????? ,????????????? cRNA ???? cRNA(complementingcRNA)?????????????? ,??? SFT? UTR????????????????[ 3] 。·58· ?????? 2004?? 35?? 1??? SFT 5'? 3'? UTR???? IRE(iron responseelement)??? ,???? SFT ??????????TfR、DML????????????? ,???? IRE-IRP(iron response protein)???????? 。?SFT 3'? UTR?? 41??? TIE???????????? ,?? ,??????????? TIE????? RNA??????? ,??? SFT ??????????? 。Yu ?[ 7] ?? , REXXE????????????????? SFT ?????????????? ,?? L2???????????SFT?? ,?????????? , REXXE ????????? ,??? SFT ?????????。?? ,SFT cDNA ? 5' ???????????????? E2(Human E2 ubiquitin-conjugating en-zyme)? UbcH5A ???? 6 / ??? 7 ?? ,UbcH5A ??? VHL ????———E3 ???????????????????????????? ,????????????????? UbcH5A????? ,?? ,Gehrke ?[ 8]?? SFT mRNA???????UbcH5A??。SFT ??????????????????。SFT ??????? 2 ????? ,?????Clox(cut-like homeobox)? CDP ???????87.5%???? ,????? v-myb ??????C/GC/TAACGG 。?? , Y????????? ,???????????????????SFT???。??????????? ,?????? SFT????????????????? Y ?????????????? 。???? ,????????SFT ?????。? 、SFT??????Barisani ???[ 6] ,???? SFT ?????;?HFE??????????? SFT ?????;??HFE????????? SFT ???? 。??????????“21??????”[ 4] ,??????????????? ,???????????????????? 、?? 、?????? 、?????????。??????? MHC(majorhistocompatibility complex)?? I ??? ———HFE ?????????????? ,??HFE??????????????????????????????????? ,??HFE??????????????????? 。??????SFT???????? SFT ???????????[ 10] ,????????????? SFT ????????5?? ,?????? SFT ???????????????????。?????????????????????????????????????? ,??????????????????????????。?? ,?????? ,SFT ?????? ,?? SFT ????????????????[ 5] ,???? SFT ??????????????????????????????? ,??????????????????????????。? ? ? ?1　Qian ZM , Tang PL.Mechanisms of iron uptake by mammaliancells.Biochim Biophy s Acta , 1995 , 1269 205～ 214.2　Qian ZM , Tang PL , Wang Q.Iron crosses the endosomal mem-brane by a carrier-mediated process.Prog Biophys Molec Biol ,1997 , 67 1 ～ 15.3　Gutierrez JA , Yu J , Rivera S , et al.Functional expressioncloning and characterization of SFT , a stimulator of Fe trans-port.J Cell Biol , 1997 , 139 895～ 905.4　Yu J , Yu ZK , Wessling-Resnick M.Expression of SFT(stimu-lator of Fe transport)is enhanced by iron chelation in HeLa cellsand by hemochromatosis in liver. J Biol Chem , 1998 ,273 34675～ 34678.5　Knutson MD , Levy JE , Andrews NC , et al.Expression of stim-ulator of Fe transport is not enhanced in Hfe knockout mice.JNutr , 2001 , 131 1459～ 1464.6　Barisani D , Parafioriti A , Armiraglio E , et al.Duodenal ex-pression of a putative stimulator of Fe transport and transferrinreceptor in anemia and hemochromatosis.Gastroenterology ,2001 , 120 1404～ 1411.7　Yu J , Wessling-Resnick M.Structural and functional analysis ofSFT , a stimulator of Fe transport. J Biol Chem , 1998 ,273 21380～ 21385.8　Gehrke SG , Riedel HD, Herrmann T , et al.UbcH5A , a mem-ber of human E2 ubiquitin-conjugating enzymes , is closely relat-ed to SFT , a stimulator of iron transport , and is up-regulated inhereditary hemochromatosis.Blood , 2003 , 101 3288 ～ 3293.9　Yu J , Wessling-Resnick M.Influence of copper depletion oniron uptake mediated by SFT , a stimulator of Fe transport.JBiol Chem , 1998 , 273 6909 ～ 6915.10　Barisani D , Conte D.Transferrin receptor 1(TfR1)and puta-tive stimulator of Fe transport(SFT) expression in Iron defi-ciency and overload:an overview.Blood Cells Mol Dis , 2002 ,29 498～ 505.·59·?????? 2004?? 35?? 1?

铁转运刺激因子研究进展

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