WAVE3 functions as a negative regulator of LDOC1

被引:18
作者
Mizutani, K
Koike, D
Suetsugu, S
Takenawa, T
机构
[1] Univ Tokyo, Inst Med Sci, Dept Biochem, Minato Ku, Tokyo 1088639, Japan
[2] JST, CREST, Minato Ku, Tokyo 1088639, Japan
关键词
apoptosis; Arp2/3; LDOC1; p53; WAVE3;
D O I
10.1093/jb/mvi160
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
WAVE3 belongs to the Wiskott-Aldrich syndrome protein family that mediates actin reorganization through activation of the Arp2/3 complex. However, the physiological function of WAVE3 is poorly understood. We found that LDOC1-encoded by a gene that is down-regrulated in tumor cell lines-binds directly to the verprolin homology domain of WAVE3. Ectopically expressed LDOC1 is localized in the nucleus and induces apoptosis in the cells. This apoptosis is accompanied by an increase in the p53 protein level, but not in p53 transcription, suggesting that LDOC1 inhibits the degradation of p53. Further, the expression of WAVE3 induces the translocation of LDOC1 from the nucleus to the cytoplasm, resulting in the inhibition of LDOC1-induced apoptosis. Thus, it is possible that the LDOC1 function is negatively regulated by WAVE3.
引用
收藏
页码:639 / 646
页数:8
相关论文
共 22 条
[11]   Identification of a novel gene, LDOC1, down-regulated in cancer cell lines [J].
Nagasaki, K ;
Manabe, T ;
Hanzawa, H ;
Maass, N ;
Tsukada, T ;
Yamaguchi, K .
CANCER LETTERS, 1999, 140 (1-2) :227-234
[12]   Heat shock induces transient p53-dependent cell cycle arrest at G1/S [J].
Nitta, M ;
Okamura, H ;
Aizawa, S ;
Yamaizumi, M .
ONCOGENE, 1997, 15 (05) :561-568
[13]   Cellular motility driven by assembly and disassembly of actin filaments [J].
Pollard, TD ;
Borisy, GG .
CELL, 2003, 112 (04) :453-465
[14]   Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein [J].
Roth, J ;
Dobbelstein, M ;
Freedman, DA ;
Shenk, T ;
Levine, AJ .
EMBO JOURNAL, 1998, 17 (02) :554-564
[15]   The ARF/p53 pathway [J].
Sherr, CJ ;
Weber, JD .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2000, 10 (01) :94-99
[16]   Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration [J].
Suetsugu, S ;
Yamazaki, D ;
Kurisu, S ;
Takenawa, T .
DEVELOPMENTAL CELL, 2003, 5 (04) :595-609
[17]   Identification of two human WAVE SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex [J].
Suetsugu, S ;
Miki, H ;
Takenawa, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 260 (01) :296-302
[18]  
Takenawa T, 2001, J CELL SCI, V114, P1801
[19]   P19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2 [J].
Tao, WK ;
Levine, AJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6937-6941
[20]   A role for ATR in the DNA damage-induced phosphorylation of p53 [J].
Tibbetts, RS ;
Brumbaugh, KM ;
Williams, JM ;
Sarkaria, JN ;
Cliby, WA ;
Shieh, SY ;
Taya, Y ;
Prives, C ;
Abraham, RT .
GENES & DEVELOPMENT, 1999, 13 (02) :152-157