Biological properties of the pml-associated nuclear bodies involved in acute promyelocytic leukaemia

Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.

Project objective

Acute promyelocytic leukaemia (APL), a disease caused by a block in promyelocyte differentiation. is associated with a t(15:17) chromosomal translocation resulting in the production of a hybrid protein, PML-RARa. which consists of a nuclear factor, PML. fused to the retinoic acid receptor a (RARa). The differentiation block is relieved by all-trans retinoic acid (RA), the activating ligand of RARa. Recently it was shown that PML is localized in distinct nuclear bodies and that PML-RARa causes disruption of these bodies together with PML s delocalization into aberrant matrix associated nuclear structures. Treatment of APL cells with RA induces a complete relocalization of PML and restores nuclear bodies. Thus the beneficial role of RA in APL might be related to its ability to restore a normal subnuclear organization. To characterize the normal function of PML-containing nuclear bodies, the major aim of the proposed work is to identify other proteins of these structures. Recombinant PML, ND/SP 100 -another protein component of nuclear bodies- and adenovirus E4ORF 3 products -also interacting with nuclear bodies- will be used as probes for the screening of an expression library to identify proteins interacting with PML. NDtSP 100 or E40RF 3. A yeast interaction trap/two-hybrid system, where PML. ND/SP 100 and E40RF 3 will serve as the bait" proteins, provides an alternative tool to isolate associated proteins."

Original text from CORDIS.

Participants

• INSTITUT PASTEUR · PARISCoordinatorFrance
• Not availableCity levelGermany

Links

• View on CORDIS