| Title |
Targeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides
|
|---|---|
| Published in |
PLOS ONE, November 2012
|
| DOI | 10.1371/journal.pone.0048636 |
| Pubmed ID | |
| Authors |
Sabine Beez, Philipp Demmer, Elena Puccetti |
| Abstract |
In acute promyelocytic leukemia (APL), hematopoietic differentiation is blocked and immature blasts accumulate in the bone marrow and blood. APL is associated with chromosomal aberrations, including t(15;17) and t(11;17). For these two translocations, the retinoic acid receptor alpha (RARα) is fused to the promyelocytic leukemia (PML) gene or the promyelocytic zinc finger (PLZF) gene, respectively. Both fusion proteins lead to the formation of a high-molecular-weight complex. High-molecular-weight complexes are caused by the "coiled-coil" domain of PML or the BTB/POZ domain of PLZF. PML/RARα without the "coiled-coil" fails to block differentiation and mediates an all-trans retinoic acid-response. Similarly, mutations in the BTB/POZ domain disrupt the high-molecular-weight complex, abolishing the leukemic potential of PLZF/RARα. Specific interfering polypeptides were used to target the oligomerization domain of PML/RARα or PLZF/RARα. PML/RARα and PLZF/RARα were analyzed for the ability to form high-molecular-weight complexes, the protein stability and the potential to induce a leukemic phenotype in the presence of the interfering peptides. Expression of these interfering peptides resulted in a reduced replating efficiency and overcame the differentiation block induced by PML/RARα and PLZF/RARα in murine hematopoietic stem cells. This expression also destabilized the PLZF/RARα-induced high-molecular-weight complex formation and caused the degradation of the fusion protein. Targeting fusion proteins through interfering peptides is a promising approach to further elucidate the biology of leukemia. |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 6% |
| Unknown | 16 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 24% |
| Professor > Associate Professor | 3 | 18% |
| Researcher | 3 | 18% |
| Student > Bachelor | 2 | 12% |
| Lecturer > Senior Lecturer | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 3 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 35% |
| Biochemistry, Genetics and Molecular Biology | 3 | 18% |
| Medicine and Dentistry | 3 | 18% |
| Psychology | 1 | 6% |
| Nursing and Health Professions | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 3 | 18% |