Journal
CANCER RESEARCH
Volume 73, Issue 14, Pages 4278-4288Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-3814
Keywords
-
Categories
Funding
- Ministry of Health, Labor, and Welfare
- Ministry of Education, Culture, Sports, Science, and Technology
- National Cancer Center Research and Development Fund
- Grants-in-Aid for Scientific Research [22130001] Funding Source: KAKEN
Ask authors/readers for more resources
The PML gene is frequently fused to the retinoic acid receptor alpha (RAR alpha) gene in acute promyelocytic leukemia (APL), generating a characteristic PML-RAR alpha oncogenic chimera. PML-RAR alpha disrupts the discrete nuclear speckles termed nuclear bodies, which are formed in PML, suggesting that nuclear body disruption is involved in leukemogenesis. Nuclear body formation that relies upon PML oligomerization and its stabilization of the hypoxia-inducible protein kinase (HIPK)-2 is disrupted by expression of the PML-RAR alpha chimera. Here, we report that disruption of nuclear bodies is also mediated by PML-RAR alpha inhibition of PML oligomerization. PKAmediated phosphorylation of PML-RAR alpha blocked its ability to inhibit PML oligomerization and destabilize HIPK2. Our results establish that both PML oligomerization and HIPK2 stabilization at nuclear bodies are important for APL cell differentiation, offering insights into the basis for the most common prodifferentiation therapies of APL used clinically. (C) 2013 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available