MOLECULAR-INTERACTIONS BETWEEN G-ACTIN, DNASE-I AND THE BETA-THYMOSINS IN APOPTOSIS - A HYPOTHESIS

The beta-thymosins are a family of <5kDa (MW), mostly acidic, proteins which were originally defined in the immune system. Recently, specifi c members of this family of cytoplasmic polypeptides, namely beta-4 an d beta-10, were shown to bind monomeric G-actin both in vitro and in v ivo. Whilst many aspects of programmed cell death or 'apoptosis' remai n to be defined, the Ca2+/Mg2+-dependent endonuclease, DNase I does fe ature in this process. Monomeric G-actin binds to and inhibits the DNA -degrading activity of DNase I. Given that the intracellular abundance of thymosins beta-4 and beta-10 is related to cell division and diffe rentiation and that anticancer/morphogenic agents such as retinoic aci d (RA) and cyclic AMP modulate expression of their respective genes, i t is possible that these G-actin sequestering proteins play significan t roles in apoptosis perhaps mediated via DNase I.