Prothymosin α plays multifunctional cell robustness roles in genomic, epigenetic, and nongenomic mechanisms

Ann N Y Acad Sci. 2012 Oct;1269:34-43. doi: 10.1111/j.1749-6632.2012.06675.x.


Prothymosin α (ProTα) possesses multiple functions for cell robustness. This protein functions intracellularly to stimulate cell proliferation and differentiation through epigenetic or genomic mechanisms. ProTα also regulates the cell defensive mechanisms through an interaction with the Nrf2-Keap1 system. Under the apoptotic conditions, it inhibits apoptosome formation by binding to Apaf-1. Regarding extracellular functions, ProTα is extracellularly released from the nucleus upon necrosis-inducing ischemia stress in a manner of nonclassical release, and thereby inhibits necrosis. However, under the condition of apoptosis, the C-terminus of ProTα is cleaved off and loses binding activity to cargo protein S100A13 for nonclassical release. However, cleaved ProTα is retained in the cytosol and inhibits apoptosome formation. ProTα was recently reported to cause immunological actions through the Toll-like receptor 4. However, the authors also suggest the possible existence of additional receptors for robust cell activities against ischemia stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptotic Protease-Activating Factor 1 / genetics
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Epigenomics*
  • Genomics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kelch-Like ECH-Associated Protein 1
  • Models, Biological
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Thymosin / analogs & derivatives*
  • Thymosin / genetics
  • Thymosin / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism


  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Protein Precursors
  • Receptors, Estrogen
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • prothymosin alpha
  • Thymosin