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Involvement of OP18 in cell proliferation
R F Melhem1, J R Strahler, N Hailat
1Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109-0510.
Abstract:
Op18 is a highly conserved major cytosolic phosphoprotein that is expressed at high levels in acute leukemia and in neuroblastoma. In this study we present evidence pointing to a role for Op18 in cellular proliferation. Blocking of Op18 mRNA translation using antisense oligonucleotides delayed entrance of mitotically stimulated normal peripheral blood lymphocytes into the S phase. Moreover treatment of HL-60 promyelocytic leukemia cells with DMSO or PMA which induced terminal differentiation resulted in a decrease in the level of Op18 RNA and protein. Inhibition of lymphoid proliferation with cyclosporin also resulted in reduced Op18 levels.
Insights
The protein Op18, crucial in cell proliferation, is downregulated during the differentiation of leukemia cells. Blocking Op18 translation delays lymphocyte proliferation, highlighting its role in cell growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Op18 is a major cytosolic phosphoprotein.
- Op18 is highly conserved and expressed at high levels in acute leukemia and neuroblastoma.
Purpose of the Study:
- To investigate the role of Op18 in cellular proliferation.
- To examine the regulation of Op18 during cell differentiation and proliferation.
Main Methods:
- Antisense oligonucleotides were used to block Op18 mRNA translation.
- HL-60 promyelocytic leukemia cells were treated with DMSO or PMA to induce differentiation.
- Lymphoid proliferation was inhibited using cyclosporin.
Main Results:
- Blocking Op18 translation delayed lymphocyte entry into the S phase.
- Treatment with DMSO or PMA decreased Op18 RNA and protein levels in HL-60 cells.
- Cyclosporin-induced inhibition of lymphoid proliferation also reduced Op18 levels.
Conclusions:
- Op18 plays a significant role in cellular proliferation.
- Op18 levels are reduced during terminal differentiation of leukemia cells.
- Op18 is a potential target for therapeutic intervention in proliferative disorders.