Journal article
PRAM-1 Is a Novel Adaptor Protein Regulated by Retinoic Acid (RA) and Promyelocytic Leukemia (PML)-RA Receptor α in Acute Promyelocytic Leukemia Cells
The Journal of biological chemistry, Vol.276(25), pp.22375-22381
06/22/2001
DOI: 10.1074/jbc.M011683200
PMID: 11301322
Abstract
The t(15;17) translocation, found in 95% of acute promyelocytic leukemia, encodes a promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) fusion protein. Complete remission of acute promyelocytic leukemia can be obtained by treating patients with all-trans retinoic acid, and PML-RARα plays a major role in mediating retinoic acid effects in leukemia cells. A main model proposed for acute promyelocytic leukemia is that PML-RARα exerts its oncogenic effects by repressing the expression of retinoic acid-inducible genes critical to myeloid differentiation. By applying subtraction cloning to acute promyelocytic leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARα target gene encoding anAdaptor Molecule-1), which encodes a novel adaptor protein sharing structural homologies with the SLAP-130/fyb adaptor. PRAM-1 is expressed and regulated during normal human myelopoiesis. In U937 myeloid precursor cells, PRAM-1 expression is inhibited by expression of PML-RARα in the absence of ligand andde novo superinduced by retinoic acid. PRAM-1 associates with other adaptors, SLP-76 and SKAP-55HOM, in myeloid cell lines and with protein tyrosine kinase lyn. By providing the first evidence that PML-RARα dysregulates expression of an adaptor protein, our data open new insights into signaling events that are disrupted during transformation by PML-RARα and induced by retinoic acid duringde novo differentiation of acute promyelocytic leukemia cells.
AJ272324
Details
- Title: Subtitle
- PRAM-1 Is a Novel Adaptor Protein Regulated by Retinoic Acid (RA) and Promyelocytic Leukemia (PML)-RA Receptor α in Acute Promyelocytic Leukemia Cells
- Creators
- Christel Moog-Lutz - InsermErik J. Peterson - UPMC Hillman Cancer CenterPierre G. Lutz - InsermSteve Eliason - Pathology andFlorence Cavé-Riant - InsermAndrew Singer - Pathology andYolande Di Gioia - InsermSally Dmowski - UPMC Hillman Cancer CenterJoanne Kamens - BASF Bioresearch Corporation, Worcester, Massachusetts 01605, and theYvon E. Cayre - Thomas Jefferson UniversityGary Koretzky - UPMC Hillman Cancer Center
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.276(25), pp.22375-22381
- Publisher
- Elsevier Inc
- DOI
- 10.1074/jbc.M011683200
- PMID
- 11301322
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 06/22/2001
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984622759602771
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