Curcumin, a natural compound, is a well-known chemopreventive agent with potent anticarcinogenic activity in a wide variety of tumor cells. Curcumin inhibits cancer cell proliferation in part by suppressing cyclin D1 and inducing expression of the cyclin-dependent kinase inhibitor p21. Both p53-dependent and p53-independent mechanisms regulate p21 expression, but the mechanism by which curcumin...

Targeting the oxygen-sensing mechanisms of the hypoxiainducible factor (HIF) pathway provides pharmacological ways of manipulating the HIF response. Because HIF-1 -specific prolyl-4 hydroxylases (PHDs) prime degradation of HIF-1 , we have made an effort to find a small molecule capable of upregulating the HIF pathway by inhibiting prolyl hydroxylation. Through an in vitro high-throughput screen...

The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) pathway is a critical intermediary for cell proliferation, differentiation and survival. In the human colon cancer cell line SW1116, treatment with the DNA methyltransferase1 (Dnmt1) inhibitor 5-aza-2’-deoxycytidine (5-aza-dC) or the ERK-MAPK inhibitors PD98059 or rottlerin, or transient transfection with the ...

Yohimbine is a potent and selective 2versus 1-adrenoceptor antagonist. To date, drugs with high specificity for the 2-adrenoceptor show marginal selectivity among the three 2-adrenoceptor subtypes. Initial studies showed that yohimbine was about 4and 15-fold more selective for the human 2C-adrenoceptor in comparison with the 2Aand 2B-adrenoceptors, respectively. To improve on this 2-adrenocepto...

In the current study, we investigated the effects of p63 modulation in epithelial plasticity in human keratinocytes. p63 isoforms ΔNp63α, ΔNp63β, and ΔNp63γ were ectopically expressed in normal human epidermal keratinocytes (NHEK). Epithelial or mesenchymal state was determined by morphological changes and altered expression of various markers, e.g., fibronectin (FN), ECadherin (E-Cad), and ker...

Although several genes have been associated with prostate cancer progression, it is clear that we are far from understanding all the molecular events implicated in the initiation and progression of the disease to a hormone-refractory state. The androgen receptor is a central player in the initiation and proliferation of prostate cancer and its response to hormone therapy. Nuclear factor-KB has ...

We have investigated the potential regulatory role of TGF-B in the interactions of neurons and Schwann cells using an in vitro myelinating system. Purified populations of neurons and Schwann cells, grown alone or in coculture, secrete readily detectable levels of the three mammalian isoforms of TGF-B; in each case, virtually all of the TGF-/~ activity detected is latent. Expression of TGF-BI, a...

Macrophages are vital to innate immunity, and express pattern recognition receptors and http://www.jbc.org/cgi/doi/10.1074/jbc.M114.614057 The latest version is at JBC Papers in Press. Published on December 23, 2014 as Manuscript M114.614057 Copyright 2014 by The American Society for Biochemistry and Molecular Biology, Inc. by gest on O cber 5, 2017 hp://w w w .jb.org/ D ow nladed from Function...

The inactive prokaryotic leu-500 promoter (Pleu-500) contains a single A-to-G point mutation in the -10 region of the leucine operon promoter, which causes leucine auxotrophy. This promoter can be activated by (-) DNA supercoiling in Escherichia coli topA strains. However, whether this activation arises from global, permanent or transient, dynamic supercoiling is still not fully understood. In ...

T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular calcium (Ca 2+ ) to activate the key transcription factors NFAT and NF-κB. The mechanism of NFAT activation by Ca 2+ has been determined; however, the role of Ca 2+ in controlling NF-κB signaling is poorly understood and the source of Ca 2+ required for NF-κB activation is unknown...