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Content archived on 2024-05-14

Functional studies on components of human nuclear domains which contain the acute promyelocytic leukaemia proto-oncoprotein pml

Objective



Research objectives and content
Acute promyelocytic leukaemia (APL) arises following a reciprocal translocation t(15;17) that fuses PML with retinoic acid receptor alpha (RARA). The PML-RARA fusion protein targets and disrupts nuclear multiprotein complexes called PODs, ND10 or NBs, a process which is associated with a block in myeloid differentiation leading to APL. The normal functions of PML NBs are presently unknown although to date twelve proteins have been identified as being part of this multi-protein nuclear complex. The proposed project is to identify further PML NB components using molecular and genetic techniques with particular emphasis on one recently identified component known as Ret Finger Protein (RFP). RFP, like PML, is oncogenic as part of a fusion protein, contains similar protein sequence motifs/domains and transiently associates with PML NBs in vivo.. The proposed studies will allow new insights into the normal functional roles of PML NBs which help our understanding of the molecular events which lead to APL.

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Coordinator

Imperial Cancer Research Fund
EU contribution
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Address
44,Lincoln's Inn Fields
WC2A 3PX London
United Kingdom

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