Thymosin beta-10 accelerates apoptosis

Cell Mol Biol Res. 1995;41(3):167-80.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / drug effects
  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • Calcimycin / pharmacology
  • Cell Division
  • DNA Damage
  • Gene Targeting
  • Ionophores / pharmacology
  • Mice
  • Microfilament Proteins / physiology
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins / metabolism
  • Thymosin / genetics
  • Thymosin / physiology*
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Actins
  • Ionophores
  • Microfilament Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Calcimycin
  • Thymosin
  • thymosin beta(10)