Oncosuppressor protein p53 and cyclin-dependent kinase inhibitor p21 regulate interstitial cystitis associated gene expression.

Interstitial cystitis (IC) is a chronic syndrome that affects the urinary bladder. The etiology of this disease is unclear, and no effective therapies are available at this time. Although inflammation is suspected, no clear evidence for a role of conventional mediators of inflammation, such as cytokines and their downstream molecules, has been obtained to date.

Tunicamycin induced endoplasmic reticulum stress promotes apoptosis of prostate cancer cells by activating mTORC1.

Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3.

Death-associated Protein Kinase-1 Expression and Autophagy in Chronic Lymphocytic Leukemia Are Dependent on Activating Transcription Factor-6 and CCAAT/Enhancer-binding Protein-β.

Expression of DAPK1, a critical regulator of autophagy and apoptosis, is lost in a wide variety of tumors, although the mechanisms are unclear. A transcription factor complex consisting of ATF6 (an endoplasmic reticulum-resident factor) and C/EBP-β is required for the IFN-γ-induced expression of DAPK1 IFN-γ-induced proteolytic processing of ATF6 and phosphorylation of C/EBP-β are obligatory for the formation of this transcriptional complex. We report that defects in this pathway fail to control growth of chronic lymphocytic leukemia (CLL).

Potential role of autophagy in the bactericidal activity of human PMNs for Bacillus anthracis.

Bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. These endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. While the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (PMNs) has not been adequately defined.

Regulation of the death-associated protein kinase 1 expression and autophagy via ATF6 requires apoptosis signal-regulating kinase 1.

The death-associated protein kinase 1 (DAPK1) is an important regulator of cell death and autophagy. Recently, we have identified that ATF6, an endoplasmic reticulum-resident transcription factor, in association with the transcription factor CEBP-β, regulates the gamma interferon (IFN-γ)-induced expression of Dapk1 (P. Gade et al.

Nicotine promotes apoptosis resistance of breast cancer cells and enrichment of side population cells with cancer stem cell-like properties via a signaling cascade involving galectin-3, α9 nicotinic acetylcholine receptor and STAT3.

Nicotine, a main addictive compound in tobacco smoke, has been linked to promotion and progression of lung, head and neck, pancreatic, and breast cancers, but the detailed mechanisms of cancer progression remain elusive. Here, we show that nicotine induces the expression of galectin-3 (an anti-apoptotic β-galactoside-binding lectin) in breast cancer cell line and in primary tumors from breast cancer patients. Nicotine-induced up regulation of galectin-3 is due to an increased expression of α9 isoform of nicotinic acetylcholine receptor (α9nAChR), which activates transcription factor STAT3 that in turn, physically binds to galectin-3 (LGALS3) promoter and induces transcription of galectin-3.

Using electronic medical records to increase the efficiency of catheter-associated urinary tract infection surveillance for National Health and Safety Network reporting.

Background: Streamlining health care-associated infection surveillance is essential for health care facilities owing to the continuing increases in reporting requirements.

Methods: Stanford Hospital, a 583-bed adult tertiary care center, used their electronic medical record (EMR) to develop an electronic algorithm to reduce the time required to conduct catheter-associated urinary tract infection (CAUTI) surveillance in adults. The algorithm provides inclusion and exclusion criteria, using the National Healthcare Safety Network definitions, for patients with a CAUTI.

The transcription factor C/EBP-β mediates constitutive and LPS-inducible transcription of murine SerpinB2.

SerpinB2 or plasminogen activator inhibitor type 2 (PAI-2) is highly induced in macrophages in response to inflammatory stimuli and is linked to the modulation of innate immunity, macrophage survival, and inhibition of plasminogen activators. Lipopolysaccharide (LPS), a potent bacterial endotoxin, can induce SerpinB2 expression via the toll-like receptor 4 (TLR4) by ∼1000-fold over a period of 24 hrs in murine macrophages. To map the LPS-regulated SerpinB2 promoter regions, we transfected reporter constructs driven by the ∼5 kb 5'-flanking region of the murine SerpinB2 gene and several deletion mutants into murine macrophages.

IFNG and autophagy: a critical role for the ER-stress mediator ATF6 in controlling bacterial infections.

IFNG/IFNγ plays a critical role in driving innate and acquired defenses against infectious pathogens. The death-associated protein kinase 1 (DAPK1), originally identified as an activator of IFNG-induced cell death, controls autophagy. Previously, we have shown that transcription factor CEBPB (C/EBP-β) regulates IFNG-induced expression of Dapk1 through a CRE/ATF motif in its enhancer.

An IFN-γ-stimulated ATF6-C/EBP-β-signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy.

The IFN family of cytokines operates a frontline defense against pathogens and neoplastic cells in vivo by controlling the expression of several genes. The death-associated protein kinase 1 (DAPK1), an IFN-γ-induced enzyme, controls cell cycle, apoptosis, autophagy, and tumor metastasis, and its expression is frequently down-regulated in a number of human tumors. Although the biochemical action of DAPK1 is well understood, mechanisms that regulate its expression are unclear.

Chromatin immunoprecipitation assay as a tool for analyzing transcription factor activity.

Differential gene expression is facilitated by transcriptional regulatory mechanisms and chromatin modifications through DNA-protein interactions. One of the widely used assays to study this is chromatin immunoprecipitation (ChIP) assay, which enables analysis of association of regulatory molecules to specific promoters and histone modifications in vivo. This is of immense value as ChIP assays can provide glimpse of the regulatory mechanisms involved in gene expression in vivo.

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

Purpose: Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis.

GRIM-1, a novel growth suppressor, inhibits rRNA maturation by suppressing small nucleolar RNAs.

We have recently isolated novel IFN-inducible gene, Gene associated with Retinoid-Interferon-induced Mortality-1 (GRIM-1), using a genetic technique. Moderate ectopic expression of GRIM-1 caused growth inhibition and sensitized cells to retinoic acid (RA)/IFN-induced cell death while high expression caused apoptosis. GRIM-1 depletion, using RNAi, conferred a growth advantage.

A central role for transcription factor C/EBP-beta in regulating CD1d gene expression in human keratinocytes.

CD1d is a nonclassical Ag-presenting molecule that presents glycolipid Ags to NKT cells that are involved in immune defense and tumor rejection. It also plays a role in immunoregulatory functions in the epidermis. The mechanisms controlling the expression of CD1d are not well understood.

Down-regulation of the transcriptional mediator subunit Med1 contributes to the loss of expression of metastasis-associated dapk1 in human cancers and cancer cells.

DAPK1, a ca(+2)/calmodulin regulated serine/threonine kinase, is a major tumor suppressor, whose expression is lost in multiple tumor types. However, the mechanisms contributing to it are unclear. We have recently shown that CCAAT/Enhancer binding protein-beta (C/EBP-beta) is required for the basal and interferon gamma (IFN-gamma)-induced expression of dapk1 in many cell types.

IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain.

Interleukin-17 (IL-17), the hallmark cytokine of T helper 17 (T(H)17) cells, signals through a distinct receptor subclass, yet little is known about the mechanisms involved. IL-17 activates the expression of target genes through the actions of the transcription factors nuclear factor kappaB (NF-kappaB), CAAT enhancer binding protein delta (C/EBPdelta), and C/EBPbeta. The adaptor proteins tumor necrosis factor receptor-associated factor 6 (TRAF6) and Act1 are upstream of NF-kappaB and C/EBPdelta, but the regulation of C/EBPbeta remains undefined.

The Med1 subunit of transcriptional mediator plays a central role in regulating CCAAT/enhancer-binding protein-beta-driven transcription in response to interferon-gamma.

Transcription factor CCAAT/enhancer-binding protein (C/EBP)-beta is crucial for regulating transcription of genes involved in a number of diverse cellular processes, including those involved in some cytokine-induced responses. However, the mechanisms that contribute to its diverse transcriptional activity are not yet fully understood. To gain an understanding into its mechanisms of action, we took a proteomic approach and identified cellular proteins that associate with C/EBP-beta in an interferon (IFN)-gamma-dependent manner.

Critical role for transcription factor C/EBP-beta in regulating the expression of death-associated protein kinase 1.

Transcription factor C/EBP-beta regulates a number of physiological responses. During an investigation of the growth-suppressive effects of interferons (IFNs), we noticed that cebpb(-/-) cells fail to undergo apoptosis upon gamma IFN (IFN-gamma) treatment, compared to wild-type controls. To examine the basis for this response, we have performed gene expression profiling of isogenic wild-type and cebpb(-/-) bone marrow macrophages and identified a number of IFN-gamma-regulated genes that are dependent on C/EBP-beta for their expression.

The interferon signaling network and transcription factor C/EBP-beta.

Cytokines like interferons (IFNs) play a central role in regulating innate and specific immunities against the pathogens and neoplastic cells. A number of signaling pathways are induced in response to IFN in various cells. One classic mechanism employed by IFNs is the JAK-STAT signaling pathway for inducing cellular responses.

A biochemical analysis of topoisomerase II alpha and beta kinase activity found in HIV-1 infected cells and virus.

Human topoisomerase II plays a crucial role in DNA replication and repair. It exists in two isoforms: topoisomerase II alpha (alpha) and topoisomerase II beta (beta). The alpha isoform is localized predominantly in the nucleus, while the beta isoform exhibits a reticular pattern of distribution both in the cytosol and in the nucleus.