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The downregulation of onzin expression by PKCepsilon-ERK2 signaling and its potential role in AML cell

S-F Wu1, Y Huang, J-K Hou

  • 1Institute of Health Science, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences-Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai, China.

Leukemia
|January 15, 2010
PubMed

Insights

Onzin protein expression decreases during acute myeloid leukemia (AML) cell differentiation, regulated by protein kinase C-epsilon (PKCepsilon)-extracellular signal-regulated protein kinase 2 (ERK2) signaling. This downregulation promotes leukemic cell monocytic differentiation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Onzin is a novel, conserved protein with poorly understood expression regulation and biological functions.
  • Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow.

Purpose of the Study:

  • To investigate the regulation of onzin expression during AML cell differentiation.
  • To elucidate the role of onzin in AML monocytic differentiation.

Main Methods:

  • Utilized AML cell lines and primary cells treated with all-trans retinoic acid (ATRA) and phorbol 12-myristate 13-acetate (PMA).
  • Employed chemical inhibitions, RNA interference, and expression of kinase mutants/forms to study signaling pathways.
  • Assessed onzin's effect on monocytic differentiation and PU.1 transcriptional activity.

Main Results:

  • Onzin expression was significantly downregulated during ATRA- and PMA-induced AML cell differentiation.
  • The protein kinase C-epsilon (PKCepsilon)-extracellular signal-regulated protein kinase 2 (ERK2) signaling pathway was essential for PMA-induced onzin downregulation.
  • Onzin suppressed PMA-induced monocytic differentiation, while its suppression enhanced differentiation.
  • Onzin interacted with and inhibited the transcriptional activity of the transcription factor PU.1.

Conclusions:

  • Phorbol 12-myristate 13-acetate (PMA) downregulates onzin expression via the PKCepsilon-ERK2 pathway.
  • Onzin acts as a negative regulator of monocytic differentiation in AML cells, partly by inhibiting PU.1 activity.

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