2015 Fiscal Year Final Research Report
The molecular mechanism that ATRA induces granulocytic differentiation in leukemic cells through the protein acetylation
| Project/Area Number |
26893264
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Keywords | PCAF / 急性前骨髄球性白血病(APL) / 全トランスレチノイン酸(ATRA) / 分化誘導療法 / ヒストンアセチル基転移酵素 / 蛋白質アセチル化 |
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| Outline of Final Research Achievements |
All-trans retinoic acid (ATRA) induces granulocytic differentiation in acute promyelocytic leukemia (APL) cells, however, its detailed molecular mechanism remains unclear. Here, we showed that the overexpression of a histone acetyltransferase PCAF induced the expression of the granulocytic differentiation marker at the mRNA level, suggesting that PCAF is essential for APL cell differentiation. In addition, we found that ATRA acetylated the PCAF substrates while ATRA induced granulocytic differentiation in leukemic cells. Furthermore, PCAF regulated the downstream target gene expression of ATRA. These observations suggested that ATRA induced granulocytic differentiation in APL cells through the PCAF-induced protein acetylation and the PCAF-regulated downstream target gene expression.
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| Free Research Field |
医師薬学
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