Phospholipid scramblase 1

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HUANG Ying()
ZHAO Qian()
CHEN Guo-Qiang()
Journal Title:
Volume 58, Issue 06, 2006
Key Word:
phospholipid scramblase 1;leukemia

Abstract: Phospholipid scramblase 1(PLSCR1)is a calcium-binding,multiply palmitoylated typeⅡ endofacial plasma membrane protein,while unpalmitoylated PLSCR 1 protein can import into the nucleus,where it binds to genomic DNA.Although the original work showed that PLSCR1 contributes to the transbilayer movement of phospholipids,the following studies revealed that PLSCR1 expression can be induced by some cytokines such as interferon,epidermal growth factor,and also by leukemic cell differentiationinducing agents such as all-trans retinoic acid(ATRA)and phorbol 12-myristate 13-acetate(PMA).PLSCR1 was also shown to interact with several protein kinases including c-Ab1,c-Src,protein kinase Cδ as well as some other proteins such as onzln,suggesting the roles of PLSCR1 in cell signaling.Indeed,the current evidence proposes that PLSCR1 contributes to cell proliferation,differentiation,apoptosis,and plays roles in the pathogenesis of cancers,especially leukemia.

  • [1]Huang Y,Zhao Q,Zhou CX,Gu ZM,Li D,Xu HZ,Sims PJ,Zhao KW,Chen GQ.Antileukemic roles of human phospholipid scramblase 1 gene,evidence from inducible PLSCR1-expressing leukemic cells.Oncogene 2006;25(50):6618-6627.
  • [2]Basse F,Stout JG,Sims PJ,Wiedmer T.Isolation of an erythro cyte membrane protein that mediates Ca2+-dependent transbilayer movement of phospholipid.J Biol Chem 1996;271(29):17205-17210.
  • [3]Zhou Q,Zhao J,Stout JG,Luhm RA,Wiedmer T,Sims PJ.Molecular cloning of human plasma membrane phospholipid scramblase.A protein mediating transbilayer movement of plasma membrane phospholipids.J Biol Chem 1997;272(29):18240-18244.
  • [4]Kasukabe T,Kobayashi H,Kaneko Y,Okabe-Kado J,Honma Y.Identity of human normal counterpart(MmTRA1b)of mouse leukemogenesis-associated gene(MmTRA1a)product as plasma membrane phospholipid scramblase and chromosome mapping of the human MmTRA1b/phospholipid scramblase gene.Biochem Biophys Res Commun 1998;249(2):449-455.
  • [5]Wiedmer T,Zhou Q,Kwoh DY,Sims PJ.Identification of three new members of the phospholipid scramblase gene family.Biochim Biophys Acta 2000;1467(1):244-253.
  • [6]Zhou Q,Zhao J,Al-Zoghaibi F,Zhou A,Wiedmer T,Silverman RH,Sims PJ.Transcriptional control of the human plasma membrane phospholipid scramblase 1 gene is mediated by interferonalpha.Blood 2000;95(8):2593-2599.
  • [7]Zhao KW,Li D,Zhao Q,Huang Y,Silverman RH,Sims PJ,Chen GQ.Interferon-alpha-induced expression of phospholipid scramblase 1 through STAT1 requires the sequential activation of protein kinase Cdelta and JNK.J Biol Chem 2005;280(52):42707-42714.
  • [8]Zhou Q,Zhao J,Wiedmer T,Sims PJ.Normal hemostasis but defective hematopoietic response to growth factors in mice deftcient in phospholipid scramblase 1.Blood 2002:99(11):4030-4038.
  • [9]Zhao KW,Li X,Zhao Q,Huang Y,Li D,Peng ZG,Shen WZ,Zhao J,Zhou Q,Chen Z,Sims PJ,Wiedmer T,Chen GQ.Protein kinase Cdelta mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression:its role in leukemic cell differentiation.Blood 2004;104(12):3731-3738.
  • [10]Sun J,Zhao J,Schwartz MA,Wang JY,Wiedmer T,Sims PJ.c-Ab1 tyrosine kinase binds and phosphorylates phospholipid scramblase 1.J Biol Chem 2001:276(31):28984-28990.
  • [11]Frank PG.Lisanti MP.Defining lipid raft structure and function withproximity imaging.Am J Physiol Heart Circ Physiol 2006;290(6):H2165-H2166.
  • [12]Langhorst MF,Reuter A,Stuermer CA.Scaffolding microdornains and beyond:the function of reggie/flotillin proteins.Cell Mol Life Sci 2005;62(19-20):2228-2240.
  • [13]Sun J,Nanjundan M,Pike LJ,Wiedmer T,Sims PJ.Plasma membrane phospholipid scramblase 1 isenriched in lipid rafts and interacts with the epidermal growth factor receptor.Biochemistry2002:41 (20):6338-6345.
  • [14]Nanjundan M,Sun J,Zhao J,Zhou Q,Sims PJ,Wiedmer T.Plasma membrane phospholipid scramblase 1 promotes EGF-dependent activation of c-Src through the epidermal growth factor receptor.J Biol Chem 2003;278(39):37413-37418.
  • [15]Frasch SC,Henson PM,Kailey JM,Richter DA,Janes MS,Fadok VA,Bratton DL.Regulation of phospholipid scramblase activity during apoptosis and cell activation by protein kinase Cdelta.J Biol Chem 2000;275(30):23065-23073.
  • [16]Pastorelli C,Veiga J,Charles N,Voignier E,Moussu H,Monteiro RC,Benhamou M.IgE receptor type Ⅰ-dependent tyrosine phosphorylation of phosphohpid scramblase.J Biol Chem 2001:276(23):20407-20412.
  • [17]Pastorelli C,Veiga J,Charles N,Voignier E,Moussu H,Monteiro R,Benhamou M.Phospholipid scramblase,a new effector of FcepsilonRI signaling in mast cells.Mol Immunol 2002;38(16-):1235-1238.
  • [18]Kametaka S,Shibata M,Moroe K,Kanamori S,Ohsawa Y,Waguri S,Sims PJ,Emoto K,Umeda M,Uchiyama Y.Identificarlon of phospholipid scramblase 1 as a novel interacting molecule with beta-secretase(beta-site amyloid precursor protein (APP)cleaving enzyme(BACE)).J Biol Chem 2003;278(17):15239-15245.
  • [19]Li Y,Rogulski K,Zhou Q,Sims PJ,Prochownik EV.The negative c-Myc target onzin affects proliferation and apoptosis Via its obligate interaction with phospholipid scramblase 1.Mol Cell Biol 2006;26(9):3401-3413.
  • [20]Rogulski K,Li Y,Rothermund K,Pu L,Watkins S,Yi F,Prochownik EV.Onzin.a c-Myc-repressed target,promotes survival and transformation by modulating the Akt-Mdm2-p53 pathway.Oncogene 2005;24(51):7524-7541.
  • [21]Wiedmer T,Zhao J,Nanjundan M,Sims PJ.Palmitoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane.Biochemistry 2003;42(5):1227-1233.
  • [22]Goldfarb DS,Corbett AH,Mason DA,Harreman MT,Adam SA.Importin alpha:a multipurpose nuclear-transport receptor.Trends Cell Biol 2004;14(9):505-514.
  • [23]Chen MH,Ben-Efraim I,Mitrousis G,Walker-Kopp N,Sims PJ,Cingolani G.Phospholipid scramblase 1 contains a nonclassical nuclear localization signal with unique binding site in importin alpha.J Biol Chem 2005;280(11):10599-10606.
  • [24]Ben.Efraim I.Zhou Q,Wiedmer T,Gerace L,Sims PJ.Phospholipid scramblase 1 is imported into the nucleus by a receptor-mediated pathway and interacts with DNA.Biochemistry 2004;43(12):3518-3526.
  • [25]Zhou Q,Ben-Efraim I,Bigcas JL,Junqueira D,Wiedmer T,Sims PJ.Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression.J Biol Chem 2005;280(41):35062-35068.
  • [26]Chen GQ,Peng ZG,Liu W,Song LP,Jiang Y,Huang Y,Zhao Q.Hypoxia inducible factor-lalpha and leukemic cell differentiation.Acta Physiol Sin(生理学报)2006;58(1):5-13.
  • [27]Iovino CS,Camacho LH.Acute myeloid leukemia:a classification and treatment update.Clin J Oncol Nurs 2003;7(5):535-540.
  • [28]Chen GQ,Shi XG,Tang W,Xiong SM,Zhu J,Cal X,Han ZG,Ni JH,Shi GY,Jia PM,Liu MM,He KL,Niu C,Ma J,Zhang P,Zhang TD,Paul P,Naoe T,Kitamura K,Miller W,Waxman S,Wang The H,Chen SJ,Chen Z.Use of arsenic trioxide (As2O3)in the treatment of acute promyelocytic leukemia(APL):I.As2O3 exerts dose-dependent dual effects on APL cells.Blood 1997;89(9):3345-3353.
  • [29]Chen GQ,Zhu J,Shi XG,Ni JH,Zhong HJ,Si GY,Jin XL,Tang W,Li XS,Xong SM,Shen ZX,Sun GL,Ma J,Zhang P,Zhang TD.Gazin C,Naoe T,Chen SJ,Wang ZY,Chen Z.In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3)in the treatment of acute promyelocytic leukemia:As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins.Blood 1996;88(3):1052-1061.
  • [30]Shen ZX,Chen GQ,Ni JH,Li XS,Xiong SM,Qiu QY,Zhu J,Tang W,Sun GL,Yang KQ,Chen Y,Zhou L,Fang ZW,Wang YT,Ma J,Zhang P,Zhang TD,Chen SJ,Chen Z,Wang ZY.Use of arsenic trioxide(As2O3)in the treatment of acute promyelocytic leukemia(APL):Ⅱ.Clinical efficacy and pharmacokinetics in relapsed patients.Blood 1997;89(9):3354-3360.
  • [31]Kasukabe T.Okabe-Kado J,Honma Y.TRA1,a novel mRNA highly expressed in leukemogenic mouse monocytic subfines but notin nonleukemogenic sublines.Blood 1997;89(8):2975-2985.
  • [32]Yokoyama A,Yamashita T,Shiozawa E,Nagasawa A,OkabeKado J.Nakamaki T,Tomoyasu S,Kimura F,Motoyoshi K,Honma Y,Kasukable T.MmTRA1b/phospholipid scramblase 1 gene expression is a new prognostic factor for acute myelogenous leukemia.Leuk Res 2004;28(2):149-157.
  • [33]Nakamaki T,Okabe-Kado J,Yamamoto-Yamaguchi Y,Hino K,Tomoyasu S,Honma Y,Kasukabe T.Role of MmTRA1b/phospholipid scramblase 1 gene expression in the induction of differentiation of human myeloid leukemia cells into granulocytes.Exp Hematol 2002;30(5):421-429.
  • [34]Yu A.McMaster CR,Byers DM,Ridgway ND,Cook HW.Stimulation of phosphatidylserine biosynthesis and facilitation of UV-induced apoptosis in Chinese hamster ovary cells overexpressing phospholipid scramblase 1.J Biol Chem 2003;278(11):9706-9714.
  • [35]Silverman RH,Halloum A,Zhou A,Dong B,A1-Zoghaibi F,Kushner D,Zhou Q,Zhao J,Wiedmer T,Sims PJ.Suppression of ovarian carcinoma cell growth in vivo by the interferoninducible plasma membrane protein,phospholipid scramblase 1.Cancer Res 2002:62(2):397-402.
  • [36]Hajra KM,Liu JR.Apoptosome dysfunction in human cancer.Apoptosis 2004;9(6):691-704.
  • [37]Danial NN,Korsmeyer SJ.Cell death:critical control points.Cell 2004;116(2):205-219.
  • [38]Song MG,Gao SM,Du KM,Xu M,Yu Y,Zhou YH,Wang Q,Chen Z,Zhu YS,Chen GQ.Nanomolar concentration of NSC606985,a camptothecin analog,induces leukemic-cell apoptosis through protein kinase Cdelta-dependent mechanisms.Blood 2005;105(9):3714-3721.
  • [39]Guo M,Song LP,Jiang Y,Liu W,Yu Y,Chen GQ.Hypoxiamimetic agents desferrioxamine and cobalt chloride induce leukemic cell apoptosis through different hypoxia-inducible factorlalpha independent mechanisms.Apoptosis 2006;11(l):67-77.
  • [40]Lu Y,Xu YB,Yuan TT,Song MG,Lubbert M,Fliegauf M,Chen GQ.Inducible expression of AML1-ETO fusion protein endows leukemic cells with susceptibility to extrinsic and intrinsic apoptosis.Leukemia 2006;20(6):987-993.
  • [41]Nusbaum P,Laine C,Seveau S,Lesavre P,Halbwachs-Mecarelli L.Early membrane events in polymorphonuclear cell(PMN) apoptosis:membrane blebbing and vesicle release,CD43 and CD16 down-regulation and phosphatidylserine externalization.Biochem Soc Trans 2004;32(Pt3):477-479.
  • [42]Fadeel B,Gleiss B,Hogstrand K,Chandra J,Wiedmer T,Sims PJ,Henter JI,Orrenius S,Samafi A.Phosphatidylserine exposure during apoptosis is a cell-type-specific event and does not correlate with plasma membrane phospholipid scramblase expression.Biochem Biophys Res Commun 1999;266(2):504-511.
  • [43]Bailey K,Cook HW,McMaster CR.The phospholipid scramblase PLSCR1 increases UV induced apoptosis primarily through the augmentation of the intrinsic apoptotic pathway and independent of direct phosphorylation by protein kinase C delta.Biochim Biophys Acta 2005;1733(2-3):199-209.
  • [44]Rami A,Sims J,Botez G,Winclder J.Spatial resolution of phosphofipid scramblase 1 (PLSCR1).caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia.Neurochem Int 2003;43(1):79-87.
  • [45]Sen GC.Viruses and interferons.Annu Rev Microbio1 2001:55:255-281.
  • [46]Der SD,Zhou A,Williams BR,Silverman RH.Identification of genes differentially regulated by interferon alpha,beta,or gamma using oligonucleotide arrays.Proc Natl Acad Sci USA 1998;95 (26):15623-15628.
  • [47]Dong B,Zhou Q,Zhao J,Zhou A,Harty RN,Bose S,Banerjee A,Slee R,Guenther J,Williams BR,Wiedmer T,Sims PJ,Silverman RH.Phospholipid scramblase 1 potentiates the antiviral activity of interferon.J Virol 2004;78(17):8983-8993.
  • [48]Wiedmer T,Zhao J,Li L,Zhou Q,Hevener A,Olefsky JM,Curtiss LK,Sims PJ.Adiposity,dyslipidemia,and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3).Proc Natl Acad Sci USA 2004;101(36):13296-13301.
  • [49]Liu J,Dai Q,Chen J,Durrant D,Freeman A,Liu T,Grossman D,Lee RM.Phospholipid scramblase 3 controls mitochondrial structure,function,and apoptotic response.Mol Cancer Res 2003;1(12):892-902.
  • [50]Frasch SC,Henson PM,Nagaosa K,Fessler MB,Borregaard N,Bratton DL.Phospholipid flip-flop and phospholipid scramblase 1(PLSCR1)co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils.J Biol Chem 2004;279(17):17625-17633.
  • [51]Acharya U,Edwards MB,Jorquera RA,Silva H,Nagashima K,Labarca P,Acharya JK.Drosophila melanogaster Scramblases modulate synaptic transmission.J Cell Biol 2006;173(1):69-82.
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