Identification of a novel Bcl-xL phosphorylation site regulating the sensitivity of taxol- or 2-methoxyestradiol-induced apoptosis

FEBS Lett. 2003 Mar 13;538(1-3):41-7. doi: 10.1016/s0014-5793(03)00131-5.

Abstract

Bcl-xL, a close homolog of Bcl2, is an important regulator of apoptosis and is overexpressed in human cancer. Phosphorylation of Bcl-xL can be induced by microtubule-damaging drugs such as taxol or 2-methoxyestradiol (2-ME). By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-ME-induced Bcl-xL phosphorylation in prostate cancer cells. Further studies with the inhibitor of Jun kinase (JNK) and phosphorylation null mutant of Bcl-xL reveal the augmentative role of JNK-mediated Bcl-xL phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of Bcl-xL by stress response kinase signaling might oppose the anti-apoptotic function of Bcl-xL to permit prostate cancer cells to die by apoptosis.

Publication types

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

MeSH terms

  • 2-Methoxyestradiol
  • Apoptosis / drug effects*
  • Base Sequence
  • DNA Primers
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Paclitaxel / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • DNA Primers
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Estradiol
  • 2-Methoxyestradiol
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Paclitaxel