PML nuclear bodies (also known as Kremer bodies, nuclear domain 10's and PML oncogenic domains, although there is nothing oncogenic about these domains since nearly all normal cells contain PML bodies) are nuclear domains which vary in size from ~0.3-1 uM and are tightly associated with a detergent-resistant nuclear component. A typical mammalian nucleus contains ~10-20 PML bodies.

The role of PML bodies is unknown. They are not major sites of transcription, they lack snRNPs and protein splicing factors and they contain little or no replicating DNA during S phase. It has been demonstrated that GFP-PML and GFP-Sp100 recover relatively slowly after photobleaching, suggesting a nuclear depot-like function for PML bodies.

Their name derives from their most intensively studied protein component, PML, which is a member of the tripartite motif (TRIM) protein family, also known as the RBCC family. This motif is composed of a RING finger, a B-box type 1 and a B-box type 2, followed by a coiled-coil region. PML was discovered through analysis of the dominant oncogene responsible for human acute promyelocytic leukemia (APL). The chromosome translocation t(15;17)(q22;q21) in APL cells fuses PML to the retinoic acid receptor a gene to form the oncoprotein PML-RARa. In APL cells, PML bodies are disrupted into a microparticulate pattern as a consequence of the expression of the PML-RARa oncoprotein. Treatment of APL cells with drugs leads to reorganization of PML to generate normal-appearing PML bodies.

In addition to the PML protein, PML bodies contain the autoantigen Sp100 and also contain CBP, p53, BLM Daxx, and others. Interestingly, these bodies are enriched for the Ubiquitin family member Sumo, which is covalently attached to PML and Sp100. Upon infection, several viral protein can also be found in PML bodies.

HeLa cell stained with DAPI and 5E10, which recognizes PML (generous gift of Roel van Driel, Amsterdam). image provide by Dr. Alfred Vertegaal