Glycogen Synthase Kinase-3 and Omi/HtrA2 Induce Annexin A2 Cleavage followed by Cell Cycle Inhibition and Apoptosis

被引:34
作者
Wang, Chi-Yun [1 ,2 ]
Lin, Yee-Shin [1 ,3 ]
Su, Wu-Chou [1 ,2 ]
Chen, Chia-Ling [3 ]
Lin, Chiou-Feng [1 ,2 ,3 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 701, Taiwan
[3] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 701, Taiwan
关键词
PROTEIN PHOSPHATASE 2A; TYROSINE PHOSPHORYLATION; MITOCHONDRIAL APOPTOSIS; MEMBRANE DYNAMICS; II EXPRESSION; LIPID RAFTS; BAX; CANCER; MCL-1; CYTOSKELETON;
D O I
10.1091/mbc.E09-02-0174
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Annexin A2 is involved in multiple cellular processes, including cell survival, growth, division, and differentiation. A lack of annexin A2 makes cells more sensitive to apoptotic stimuli. Here, we demonstrate a potential mechanism for apoptotic stimuli-induced annexin A2 cleavage, which contributes to cell cycle inhibition and apoptosis. Annexin A2 was persistently expressed around the proliferative but not the necrotic region in BALB/c nude mice with human lung epithelial carcinoma cell A549-derived tumors. Knockdown expression of annexin A2 made cells susceptible to either serum withdrawal-induced cell cycle inhibition or cisplatin-induced apoptosis. Under apoptotic stimuli, annexin A2 was time-dependently cleaved. Mechanistic studies have shown that protein phosphatase 2A (PP2A)-activated glycogen synthase kinase (GSK)-3 is essential for this process. Therefore, inhibiting GSK-3 reversed serum withdrawal-induced cell cycle inhibition and cisplatin-induced apoptosis. Furthermore, inhibiting serine proteases blocked apoptotic stimuli-induced annexin A2 cleavage. Bax activation and Mcl-1 destabilization, which is regulated by PP2A and GSK-3, caused annexin A2 cleavage via an Omi/HtrA2-dependent pathway. Taking these results together, we conclude that GSK-3 and Omi/HtrA2 synergistically cause annexin A2 cleavage and then cell cycle inhibition or apoptosis.
引用
收藏
页码:4153 / 4161
页数:9
相关论文
共 41 条
[1]   Annexins in cell membrane dynamics:: Ca2+-regulated association of lipid microdomains [J].
Babiychuk, EB ;
Draeger, A .
JOURNAL OF CELL BIOLOGY, 2000, 150 (05) :1113-1123
[2]   Modulating signaling events in smooth muscle: cleavage of annexin 2 abolishes its binding to lipid rafts [J].
Babiychuk, EB ;
Monastyrskaya, K ;
Burkhard, FC ;
Wray, S ;
Draeger, A .
FASEB JOURNAL, 2002, 16 (10) :1177-1184
[3]  
CHEN J, 1994, J BIOL CHEM, V269, P7957
[4]   REGULATION OF PROTEIN SERINE-THREONINE PHOSPHATASE TYPE-2A BY TYROSINE PHOSPHORYLATION [J].
CHEN, J ;
MARTIN, BL ;
BRAUTIGAN, DL .
SCIENCE, 1992, 257 (5074) :1261-1264
[5]   Specific down-regulation of annexin II expression in human cells interferes with cell proliferation [J].
Chiang, YP ;
Rizzino, A ;
Sibenaller, ZA ;
Wold, MS ;
Vishwanatha, JK .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1999, 199 (1-2) :139-147
[6]   INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].
CROSS, DAE ;
ALESSI, DR ;
COHEN, P ;
ANDJELKOVICH, M ;
HEMMINGS, BA .
NATURE, 1995, 378 (6559) :785-789
[7]   Selective degradation of annexins by chaperone-mediated autophagy [J].
Cuervo, AM ;
Gomes, AV ;
Barnes, JA ;
Dice, JF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (43) :33329-33335
[8]   An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface [J].
Deora, AB ;
Kreitzer, G ;
Jacovina, AT ;
Hajjar, KA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (42) :43411-43418
[9]   ANNEXIN-II IS A MAJOR COMPONENT OF FUSOGENIC ENDOSOMAL VESICLES [J].
EMANS, N ;
GORVEL, JP ;
WALTER, C ;
GERKE, V ;
KELLNER, R ;
GRIFFITHS, G ;
GRUENBERG, J .
JOURNAL OF CELL BIOLOGY, 1993, 120 (06) :1357-1369
[10]  
Emoto K, 2001, ANTICANCER RES, V21, P1339