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Content archived on 2024-05-14

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

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.

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INSTITUT PASTEUR
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Rue du Docteur Roux 28
75724 Paris
France

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