Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML.
The ret finger protein (rfp) is a member of the B-box zinc finger gene family many of which may function in growth regulation and in the appropriate context become oncogenic. Members of this family are nuclear proteins that possess a characteristic tripartite motif consisting of the RING and B-box zinc binding domains and a coiled-coil domain. The promyelocytic leukemia gene (PML), another B-box family member, produces a protein product that is detected within punctate nuclear structures called PML nuclear bodies (NBs) or PML oncogenic domains (PODs). These NBs are complex structures that consist of a number of different proteins many of which have yet to be identified. In the disease acute promyelocytic leukemia (APL) a fusion protein, PML-RARA, is produced through the t(15:17) translocation. In APL the morphology of the NBs is altered. We report that rfp co-localizes with PML in a subset of the PML NBs and that it interacts directly with PML. This interaction is mediated through the rfp B-box and the distal two coils. In contrast, homomultimerization of rfp preferentially involves the B-box and the proximal coil. The association of rfp with the PML NBs is altered by mutations that affect rfp/PML interaction and in NB4 cells that are derived from APL patients. When treated with retinoic acid, rfp reassociates with the NBs in a pattern similar to non APL cells. Additionally, we found that rfp colocalizes with PML-RARA protein produced in APL patients. These results suggest that rfp, along with the other known/unknown components of PML NBs, have an important role in regulating cellular growth and differentiation.
Pubmed ID: 9570750 RIS Download
Amino Acid Sequence | Antineoplastic Agents | Cell Differentiation | Cell Division | Cell Nucleus | DNA-Binding Proteins | Fibrosarcoma | Gene Expression Regulation, Neoplastic | Humans | Leukemia, Promyelocytic, Acute | Molecular Sequence Data | Mutagenesis | Neoplasm Proteins | Nuclear Proteins | Promyelocytic Leukemia Protein | Protein Binding | Recombinant Proteins | Transcription Factors | Transfection | Tretinoin | Tumor Cells, Cultured | Tumor Suppressor Proteins | Zinc Fingers