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.
Cao
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T
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030, USA.
Duprez
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Borden
K L
KL
Freemont
P S
PS
Etkin
L D
LD
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D005354:Fibrosarcoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000502:physiology; D025521:Tumor Suppressor Proteins; D016335:Zinc Fingers / Q000235:genetics; D000070584:Tripartite Motif Proteins
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011994:Recombinant Proteins; D014157:Transcription Factors; D014212:Tretinoin; D025521:Tumor Suppressor Proteins; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins; C070576:PML protein, human