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Involvement of nPKC-MAPK pathway in the decrease of nucleophosmin/B23 during megakaryocytic differentiation of human

Chih-Chung Chou1, Benjamin Yat-Ming Yung, Chen-Ya Hsu

  • 1Department and Graduate School of Biotechnology, Fooyin University, 151 Chin-Hsueh, Rd., Ta-Liao Hsiang, Kaohsiung Hsien, 831 Taiwan, ROC.

Life Sciences
|April 24, 2007
PubMed

Insights

Proteasome inhibitors prevented the decrease of nucleophosmin/B23 (NPM/B23) protein during TPA-induced megakaryocytic differentiation. The novel PKC-MAPK pathway is essential for NPM/B23 downregulation in this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Human myelogenous leukemia K562 cells differentiate into megakaryocytes upon phorbol ester (TPA) treatment.
  • Nucleophosmin/B23 (NPM/B23), a key nucleolar protein, is downregulated during this differentiation process.

Purpose of the Study:

  • To investigate the signaling pathways regulating NPM/B23 protein downregulation during TPA-induced megakaryocytic differentiation.
  • To determine the role of proteasomes and specific kinases (PKC, MAPK) in NPM/B23 regulation.

Main Methods:

  • K562 cells were treated with TPA, proteasome inhibitors, PKC inhibitors (GF109203X, Gö 6976), and MEK1 inhibitor (PD98059).
  • Protein levels of NPM/B23 and nucleolin were analyzed using Western blotting.
  • Megakaryocytic differentiation was assessed morphologically and by protein markers.

Main Results:

  • Proteasome inhibitors blocked the TPA-induced decrease of NPM/B23.
  • The novel PKC inhibitor GF109203X, but not Gö 6976, blocked NPM/B23 decrease.
  • MEK1 inhibitor PD98059 blocked NPM/B23 decrease and megakaryocytic differentiation, but not cell growth arrest.
  • NPM/B23 downregulation was more closely linked to novel PKC-MAPK signaling than nucleolin degradation.

Conclusions:

  • The novel PKC-MAPK pathway is crucial for the downregulation of NPM/B23 during TPA-induced megakaryocytic differentiation of K562 cells.
  • Proteasomes are involved in the degradation of NPM/B23 during this process.

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