The interaction between E-tropomodulin and thymosin beta-10 rescues tumor cells from thymosin beta-10 mediated apoptosis by restoring actin architecture.
Thymosin beta-10 (TB10) is a small G-actin binding protein that induces depolymerization of intracellular F-actin pools by sequestering actin monomers. Previously, we demonstrated that overexpression of TB10 in ovarian tumor cells increased the rate of cell death. As an initial step to define molecular mechanism of TB10-dependent apoptotic process in ovarian tumor cells, we searched a human ovary cDNA library for a novel TB10 binding protein using a yeast two-hybrid system. The selected protein was human E-tropomodulin (E-Tmod), another component of the actin binding proteins. Subsequently, two interacting protein components were determined quantitatively. Results showed that the full-length TB10 is required to bind with E-Tmod, and the TB10 binding site on E-Tmod partially overlaps with the actin binding site on E-Tmod. Moreover, introduction of E-Tmod cDNA into a tumor cell line reversed TB10 mediated apoptosis and restored actin architectures. These results may suggest that TB10 regulates apoptotic homeostasis by not only just binding to actin but also competing or blocking the protein complex formation of E-Tmod with actin.
Rho
Seung Bae
SB
Molecular Therapy Research Center, Sungkyunkwan University, Samsung Medical Center Annex 8F, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, South Korea.
Chun
Taehoon
T
Lee
Seung-Hoon
SH
Park
Kyoungsook
K
Lee
Je-Ho
JH
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D015723:Gene Library; D006801:Humans; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013947:Thymosin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051348:Tropomodulin; D014407:Tumor Cells, Cultured
D000199:Actins; D002352:Carrier Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C495829:TMOD1 protein, human; D051348:Tropomodulin; D013947:Thymosin; C039302:thymosin beta(10)