PML nuclear bodies (NBs) are involved in the regulation of key nuclear pathways but their biochemical function in nuclear metabolism is unknown. In this study PML NB assembly dynamics were assessed by live cell imaging and mathematic modeling of its major component parts. We show that all six nuclear PML isoforms exhibit individual exchange rates at NBs and identify PML V as a scaffold subunit....

Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL). The mechanism by which this agent cures this disease was previously shown to involve direct interactions between ATO and the promyelocytic leukemia protein (PML), as well as accelerated degradation of the APL-associated fusion oncoprotein PML/retinoic acid receptor α ...

The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent ...

AIMS Hyperaldosteronism is associated with vascular injury and increased cardiovascular events. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular homeostasis. We hypothesized that hyperaldosteronism impairs EPC function and vascularization capacity in mice and humans. METHODS AND RESULTS We characterized the effects of aldosteron...

Abstract We aim to analyze and calculate time-dependent acoustic wave scattering by a bounded obstacle locally perturbed non-selfintersecting curve. The problem is equivalently reformulated as an initial-boundary value of the equation in truncated domain through well-defined transparent boundary condition. Well-posedness stability reduced are established. Numerically, we adopt perfect matched l...

Here we demonstrate that endogenous human homeodomain-interacting protein kinase (HIPK) 2 and the highly homologous kinase HIPK3 are found in a novel subnuclear domain, the HIPK domains. These are distinct from other subnuclear structures such as Cajal bodies and nucleoli and show only a partial colocalization with promyelocytic leukemia (PML) nuclear bodies (PML-NBs). A kinase inactive HIPK2 p...

Mdm2 is a nucleoplasmic and nucleolar protein interacting with p53 and alternative reading frame (ARF) tumor suppressor proteins. Here we demonstrate relocalization and novel interactions of Mdm2 with the promyelocytic leukemia (PML) protein following cellular stress and DNA damage. We show that Mdm2 and PML interact directly in vivo and in vitro depending on the Mdm2 RING finger domain and the...

Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia alpha gene (PML) with retinoic acid receptor gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in...

Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitati...

The promyelocytic leukemia (PML) gene, a tumor suppressor inactivated in acute promyelocytic leukemia (APL), regulates apoptosis induced by DNA damage. However, the molecular mechanisms by which PML modulates apoptosis following genotoxic stress are only partially elucidated. PML is essential for p53-dependent induction of programmed cell death upon gamma-irradiation through PML-nuclear body (N...