Dual regulation of Stat1 and Stat3 by the tumor suppressor protein PML contributes to interferon α-mediated inhibition of angiogenesis.

IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angioproliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis.

Control of antioxidative response by the tumor suppressor protein PML through regulating Nrf2 activity.

Oxidative stress is a consequence of an imbalance between reactive oxygen species (ROS) production and the ability of the cytoprotective system to detoxify the reactive intermediates. The tumor suppressor promyelocytic leukemia protein (PML) functions as a stress sensor. Loss of PML results in impaired mitochondrial complex II activity, increased ROS, and subsequent activation of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidative pathway.

Ablation of promyelocytic leukemia protein (PML) re-patterns energy balance and protects mice from obesity induced by a Western diet.

The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Mice with a deletion in the gene for PML (KO mice) exhibit altered gene expression in liver, adipose tissue, and skeletal muscle, an accelerated rate of fatty acid metabolism, abnormal glucose metabolism, constitutive AMP-activating kinase (AMPK) activation, and insulin resistance in skeletal muscle. Last, an increased rate of energy expenditure protects PML KO mice from the effects of obesity induced by a Western diet.

Microarray analyses of glucocorticoid and vitamin D3 target genes in differentiating cultured human podocytes.

Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor) and vitamin D3 (ligand for vitamin D receptor) protect or promote repair of podocytes from injury.

Post-translational modifications of PML: consequences and implications.

The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies. Emerging evidences indicated that PML actively participates in many aspects of cellular processes, but the molecular mechanisms underlying PML regulation in response to stress and environmental cues are not complete. Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML.

Microarray analysis revealing common and distinct functions of promyelocytic leukemia protein (PML) and tumor necrosis factor alpha (TNFα) signaling in endothelial cells.

Background: Promyelocytic leukemia protein (PML) is a tumor suppressor that is highly expressed in endothelial cells nonetheless its role in endothelial cell biology remains elusive. Tumor necrosis factor alpha (TNFα) is an important cytokine associated with many inflammation-related diseases. We have previously demonstrated that TNFα induces PML protein accumulation.

Promyelocytic leukemia protein (PML) regulates endothelial cell network formation and migration in response to tumor necrosis factor α (TNFα) and interferon α (IFNα).

Promyelocytic leukemia protein (PML) is a tumor suppressor that is highly expressed in vascular endothelium and inflamed tissues, yet its role in inflammation-associated cytokine-regulated angiogenesis and underlying mechanism remains largely unclear. We show that tumor necrosis factor α (TNFα) and interferon α (IFNα) stimulate PML expression while suppressing EC network formation and migration, two key events during angiogenesis. By a knockdown approach, we demonstrate that PML is indispensable for TNFα- and IFNα-mediated inhibition of EC network formation.

The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells.

Alpha actinins (ACTNs) are known for their ability to modulate cytoskeletal organization and cell motility by cross-linking actin filaments. We show here that ACTN4 harbors a functional LXXLL receptor interaction motif, interacts with nuclear receptors in vitro and in mammalian cells, and potently activates transcription mediated by nuclear receptors. Whereas overexpression of ACTN4 potentiates estrogen receptor α (ERα)-mediated transcription in transient transfection reporter assays, knockdown of ACTN4 decreases it.

G protein pathway suppressor 2 (GPS2) is a transcriptional corepressor important for estrogen receptor alpha-mediated transcriptional regulation.

We have identified G protein suppressor 2 (GPS2) as a stable component of the SMRT corepressor complexes. GPS2 potently represses basal transcription, with the repression domain mapped to the N-terminal silencing mediator of retinoic acid and thyroid hormone receptor (SMRT)-interacting domain. Knockdown of GPS2 abrogates, whereas overexpression potentiates, SMRT-mediated repression activity.

Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body formation.

Promyelocytic leukemia protein (PML) sumoylation has been proposed to control the formation of PML nuclear bodies (NBs) and is crucial for PML-dependent cellular processes, including apoptosis and transcriptional regulation. However, the regulatory mechanisms of PML sumoylation and its specific roles in the formation of PML NBs remain largely unknown. Here, we show that histone deacetylase 7 (HDAC7) knockdown reduces the size and the number of the PML NBs in human umbilical vein endothelial cells (HUVECs).

Signal-dependent regulation of transcription by histone deacetylase 7 involves recruitment to promyelocytic leukemia protein nuclear bodies.

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are dynamic subnuclear compartments that play roles in several cellular processes, including apoptosis, transcriptional regulation, and DNA repair. Histone deacetylase (HDAC) 7 is a potent corepressor that inhibits transcription by myocyte enhancer factor 2 (MEF2) transcription factors. We show here that endogenous HDAC7 and PML interact and partially colocalize in PML NBs.

The recombinant immunogen with high-density epitopes of ELDKWA and ELDEWA induced antibodies recognizing both epitopes on HIV-1 gp41.

The high mutation rate of HIV-1 (human immunodeficiency virus-1) is a major obstacle to developing an effective vaccine. The mutation of ELDKWA-(aa669-674) to ELDEWA-epitope on HIV-1 gp41 caused the immune escape from neutralization by potent anti-HIV-1 human monoclonal antibody (mAb) 2F5. In this study, we suggested and evaluated a multi-epitope vaccine as a new strategy to develop HIV-1 vaccines.