Antiapoptosis potential of bcl-2 oncogene by dephosphorylation

Biochem Cell Biol. Nov-Dec 1994;72(11-12):455-62. doi: 10.1139/o94-061.

Abstract

The antiapoptosis potential of bcl-2 has now been well established. But the biochemical mechanism of bcl-2 action is still poorly understood. Using the phosphatase inhibitor okadaic acid (OA) or chemotherapeutic agents such as Taxol and 5'-fluorouracil, we found that bcl-2 can be phosphorylated. Since OA or Taxol treatment leads to apoptosis, it seems that phosphorylation of bcl-2 leads to its inactivation. Exposure of several lymphoid cell lines expressing differential amounts of bcl-2 protein to OA resulted in apoptosis of the cells and hyperphosphorylation of bcl-2. Interestingly, the lymphoblastoid cell lines that did not phosphorylate bcl-2 following OA exposure did not undergo apoptosis. Moreover, pro-B cells isolated from patients with acute lymphoblastic leukemias exhibited endogenous phosphorylated forms of bcl-2 and a large number of apoptotic cells, even without OA treatment. Treatment with the phosphatase inhibitor or with chemotherapeutic agents (Taxol, 5'-fluorouracil) led to severe apoptosis of these cells, along with hyperphosphorylation of bcl-2. Phosphoamino acid analysis reveals that bcl-2 is phosphorylated at a serine residue. In summary, our investigation indicates that the phosphorylation pathway involving bcl-2 can be the determinant of cell death in lymphocytes.

Publication types

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

MeSH terms

  • Apoptosis / genetics*
  • Ethers, Cyclic / pharmacology
  • Fluorescent Dyes
  • Fluorouracil / pharmacology
  • Humans
  • Lymphocytes / metabolism
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology
  • Okadaic Acid
  • Paclitaxel / pharmacology
  • Phosphorylation
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogenes*
  • Tumor Cells, Cultured

Substances

  • Ethers, Cyclic
  • Fluorescent Dyes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Okadaic Acid
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Paclitaxel
  • Fluorouracil