A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein

Jacqueline A. Dyck, Gerd G. Maul, Wilson H. Miller, J. Don Chen, Akira Kakizuka, Ronald M. Evans

Research output: Contribution to journalArticle

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Abstract

Acute promyelocytic leukemia (APL) is associated with a t(15; 17) translocation that creates the promyelocyte-retinoic acid receptor α (PML-RARα) fusion gene. Immunohistochemistry demonstrates that PML is a part of a novel macromolecular organelle (including at least three other nuclear proteins) referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted into a microparticulate pattern as a consequence of the expression of the PML-RAR oncoprotein. RA treatment of APL cells triggers a reorganization of PML to generate normal-appearing PODs. We propose that PML-RAR is a dominant negative oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel structure, but it can be ascribed an imputed function such that its disruption leads to altered myeloid maturation; this may represent a novel oncogenic target.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalCell
Volume76
Issue number2
DOIs
StatePublished - Jan 28 1994

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Granulocyte Precursor Cells
Acute Promyelocytic Leukemia
Retinoic Acid Receptors
Oncogene Proteins
Gene Fusion
Nuclear Proteins
Organelles
Fusion reactions
Genes
Immunohistochemistry
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dyck, Jacqueline A. ; Maul, Gerd G. ; Miller, Wilson H. ; Chen, J. Don ; Kakizuka, Akira ; Evans, Ronald M. / A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. In: Cell. 1994 ; Vol. 76, No. 2. pp. 333-343.
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A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. / Dyck, Jacqueline A.; Maul, Gerd G.; Miller, Wilson H.; Chen, J. Don; Kakizuka, Akira; Evans, Ronald M.

In: Cell, Vol. 76, No. 2, 28.01.1994, p. 333-343.

Research output: Contribution to journalArticle

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