Thymosin beta-10 accelerates apoptosis.
The 5 Kd (MW), retinoic acid responsive thymosin beta-10 protein is expressed at relatively high levels in embryonic tissues, and its mRNA is abundant in a variety of tumors and tumor cell lines. Recently this protein (together with other members of the same protein family) was found to be a major intracellular G-actin binding protein. In the present study, plasmid-driven overexpression of thymosin beta-10 gene results in increased susceptibility of permanently transfected fibroblasts to undergo apoptosis. Conversely, knockout of the endogenous gene via overexpression of the antisense mRNA inhibited cell death induced by TNF-alpha and calcium ionophore A23187. Differential expression of thymosin beta-10 influenced cell proliferation, cell morphology, and expression/distribution of the antiapoptotic protein bcl-2. The presence of increased cytoplasmic thymosin beta-10 precipitated significant disruption of phalloidin-stained actin stress fibers while knockout of thymosin expression promoted F-actin assembly. These and other observations suggest that thymosin beta-10 (a) plays a significant and possibly obligatory role in cellular processes controlling apoptosis possibly by acting as an actin-mediated tumor suppressor, (b) perhaps functions as a neoapoptotic influence during embryogenesis, and (c) may mediate some of the pro-apoptotic anticancer actions of retinoids.
Hall
A K
AK
Department of Pharmacology, University of Cambridge, UK.
D016475:3T3 Cells / Q000187:drug effects; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division; D004249:DNA Damage; D018390:Gene Targeting; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000378:metabolism; D013947:Thymosin / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000199:Actins; D007476:Ionophores; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D013947:Thymosin; C039302:thymosin beta(10)