WAVE3 functions as a negative regulator of LDOC1.
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-regulated 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.
Mizutani
Kiyohito
K
Department of Biochemistry, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639.
Koike
Daisuke
D
Suetsugu
Shiro
S
Takenawa
Tadaomi
T
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
C120625:LDOC1 protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D001973:Bromodeoxyuridine