Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl acyltransferase

被引:93
作者
Ducker, CE [1 ]
Stettler, EM [1 ]
French, KJ [1 ]
Upson, JJ [1 ]
Smith, CD [1 ]
机构
[1] Penn State Univ, Dept Pharmacol, Coll Med, Hershey, PA 17033 USA
关键词
palmitoylation; protein; palmitoyl acyltransferase; RAS; intracellular signaling;
D O I
10.1038/sj.onc.1208171
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein palmitoyltransferases (PATs) represent an exciting new target for anticancer drug design due to their pivotal roles in the subcellular localization of a number of oncogenes. We show that the Huntingtin interacting protein 14 (HIP14) is a PAT with a preference for the farnesyl-dependent palmitoylation motif found in H- and N-RAS. Characterization of HIP14 in mouse cells has revealed that it has the ability to induce colony formation in cell culture, anchorage-independent growth, and tumors in mice. Activity of the enzyme and its ability to transform cells is dependent on critical residues in the active site of the enzyme.
引用
收藏
页码:9230 / 9237
页数:8
相关论文
共 39 条
[31]   DOUBLY-LIPID-MODIFIED PROTEIN-SEQUENCE MOTIFS EXHIBIT LONG-LIVED ANCHORAGE TO LIPID BILAYER-MEMBRANES [J].
SHAHINIAN, S ;
SILVIUS, JR .
BIOCHEMISTRY, 1995, 34 (11) :3813-3822
[32]   CYSTEINE(3) OF SRC FAMILY PROTEIN-TYROSINE KINASES DETERMINES PALMITOYLATION AND LOCALIZATION IN CAVEOLAE [J].
SHENOYSCARIA, AM ;
DIETZEN, DJ ;
KWONG, J ;
LINK, DC ;
LUBLIN, DM .
JOURNAL OF CELL BIOLOGY, 1994, 126 (02) :353-363
[33]   Functional rafts in cell membranes [J].
Simons, K ;
Ikonen, E .
NATURE, 1997, 387 (6633) :569-572
[34]   HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis [J].
Singaraja, RR ;
Hadano, S ;
Metzler, M ;
Givan, S ;
Wellington, CL ;
Warby, S ;
Yanai, A ;
Gutekunst, CA ;
Leavitt, BR ;
Yi, H ;
Fichter, K ;
Gan, L ;
McCutcheon, K ;
Chopra, V ;
Michel, J ;
Hersch, SM ;
Ikeda, JE ;
Hayden, MR .
HUMAN MOLECULAR GENETICS, 2002, 11 (23) :2815-2828
[35]  
Smart EJ, 1999, MOL CELL BIOL, V19, P7289
[36]   p260/270 expressed in embryonic abdominal leg cells of Bombyx mori can transfer palmitate to peptides [J].
Ueno, K ;
Suzuki, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13519-13526
[37]   Characterization of human palmitoyl-acyl transferase activity using peptides that mimic distinct palmitoylation motifs [J].
Varner, AS ;
Ducker, CE ;
Xia, ZP ;
Zhuang, Y ;
De Vos, ML ;
Smith, CD .
BIOCHEMICAL JOURNAL, 2003, 373 :91-99
[38]   A fluorescence-based high performance liquid chromatographic method for the characterization of palmitoyl acyl transferase activity [J].
Varner, AS ;
De Vos, ML ;
Creaser, SP ;
Peterson, BR ;
Smith, CD .
ANALYTICAL BIOCHEMISTRY, 2002, 308 (01) :160-167
[39]   Innovative treatment programs against cancer - I. Ras oncoprotein as a molecular target [J].
Waddick, KG ;
Uckun, FM .
BIOCHEMICAL PHARMACOLOGY, 1998, 56 (11) :1411-1426