Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML

Tongyu Cao, Estelle Duprez, Katherine L.B. Borden, Paul S. Freemont, Laurence D. Etkin

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1319-1329
Number of pages11
JournalJournal of Cell Science
Volume111
Issue number10
StatePublished - Jun 26 1998

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Keywords

  • Acute promyelocytic leukemia
  • B-box
  • Differentiation
  • PML
  • rfp
  • RING finger
  • Zinc finger

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cao, T., Duprez, E., Borden, K. L. B., Freemont, P. S., & Etkin, L. D. (1998). Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML. Journal of Cell Science, 111(10), 1319-1329.