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, specific members of this family of cytoplasmic polypeptides, namely beta-4 and beta-10, were shown to bind monomeric G-actin both in vitro and in vivo. Whilst many aspects of programmed cell death or 'apoptosis' remain to be defined, the Ca2+/Mg(2+)-dependent endonuclease, DNase I does feature 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 differentiation and that anticancer/morphogenic agents such as retinoic acid (RA) and cyclic AMP modulate expression of their respective genes, it is possible that these G-actin sequestering proteins play significant roles in apoptosis perhaps mediated via DNase I.
Hall
A K
AK
Department of Pharmacology, University of Cambridge, UK.
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle; D016923:Cell Death; D002454:Cell Differentiation; D003850:Deoxyribonuclease I / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010684:Philosophy; D013947:Thymosin / Q000378:metabolism*
D000199:Actins; D013947:Thymosin; D003850:Deoxyribonuclease I