One of the conclusions of our report1 is that PML/RARa itself mediates RA-dependent differentiation and that its degradation by RAis not crucial for the differentiation process to occur. Naoe and Kitamura disagree. In general, we think that there is much direct and indirect evidence to support these conclusions: (1) PML/RARa is an RA-dependent transcriptional activator2,3; (2) PML/RARa mediates...

Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infected cells in vivo. Varicella-zoster virus (VZV) is a human alphaherpesvirus t...

PML/RARA, a potent transcriptional inhibitor of nuclear receptor signaling, represses myeloid differentiation genes and drives acute promyelocytic leukemia (APL). Association of the retinoid X receptor-α (RXRA) coreceptor to PML/RARA is required for transformation, with RXRA promoting its efficient DNA binding. APL is exquisitely sensitive to retinoic acid (RA) and arsenic trioxide (arsenic), w...

P romyelocytic leukemia nuclear bodies (PML NBs) are nucleoplasmic particles that contain numerous proteins , including the PML protein itself. In patients with promyelocytic leukemia, PML is fused to retinoic acid receptor ␣, resulting in a loss of PML NBs and a block in promy-elocyte differentiation. Yet the precise function of PML NBs remains unclear. To learn more about these particles, Chi...

PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these d...

Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multistep targeting of newly synthesized epitope-tagged H3.3 to chromatin via PML bodies. H3.3 is recruited to PML bodies in a DAXX-dependent manner, a process facilitated by ASF1A. DAXX is required for enrichment of ATRX, but not ASF1A or HIRA, with PML. Nonetheless, the chaperon...

Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to treat heart failure, have garnered recent attention as potential anti-cancer and anti-viral agents. A high-throughput phenotypic screen designed to identify modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that mul...

The transcription coactivator and histone acetyltransferase CAMP response element-binding protein (CBP) has been demonstrated to accumulate in promyelocytic leukemia (PML) bodies. We show that this accumulation is cell type specific. In cells where CBP does not normally accumulate in PML bodies, it can be induced to accumulate in PML bodies through overexpression of either CBP or Pml, but not S...

Surmounting multiple tumor suppressive barriers is fundamental to cancer onset, but also predicts that their restoration may pose a powerful anticancer strategy. The proof of this principle has been elegantly demonstrated by the restoration of p53-induced tumor suppression (reviewed in ref. 1). The promyelocytic leukemia protein (PML) is emerging as a key tumor suppressor that is inactivated in...

BACKGROUND Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). In addition, RA acts as a natural morphogen in neural development. OBJECTIVES This study aimed to examine PML gene expression in different stages of in vitro neural differentiation of NT2 cells, and to investigate the possible role o...