Regulation of inducible gene expression by the transcription factor NF-kappaB.
The transcription factor NF-kappaB plays a critical role in regulating inducible gene expression in immune responses. The activation of NF-kappaB is regulated at multiple levels, probably reflecting a need to maintain a tight control of its activity. We have recently discovered that direct phosphorylation of NF-kappaB itself is essential for its transcriptional activity and that phosphorylation acts as a switch to determine association of nuclear NF-kappaB with histone acetylases vs deacetylases.

title: New regulators of NF-κB in inflammation
abstract: Research on the biological function of nuclear factor-κB (NF-κB), a key mediator of inducible transcription in the immune system, has traditionally focused on its role in the initiation of innate and adaptive immune responses. These studies have largely concentrated on the mechanisms of signalling that lead to NF-κB activation and on the positive role of NF-κB in both physiological immunity and pathological inflammation. More recently, there has been growing interest in the mechanisms that directly regulate the NF-κB transcriptional programmes. As a result, several new NF-κB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-κB.

title: Missing Pieces in the NF-κB Puzzle
abstract: The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.

title: Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal.
abstract: The DNA binding subunit of the transcription factor NF-kappa B, p50, has been cloned. p50 appears to be synthesized as a larger protein that is then processed to its functional size. Sequence analysis reveals remarkable homology for over 300 amino acids at the amino-terminal end to the oncogene v-rel, its cellular homolog c-rel, and the Drosophila maternal effect gene dorsal. This establishes NF-kappa B as a member of the rel family of proteins, all of which display nuclear-cytosolic translocation. Protein sequence from the p65 polypeptide has established that it is not encoded in the same mRNA as p50. However, p65 appears homologous to c-rel, suggesting that c-rel may form heterodimers with p50 and rel may include a homodimerization motif.

title: Volatilization of Mercury by Resting Mercury-Resistant Bacterial Cells

abstract: The mercuric ion reduction system encoded by the Hg2+ inducible mer operon confers bacterial resistance to mercuric ion. The mer A gene product which is a FAD-containing enzyme catalyzes the reduction of Hg2+ to volatile elemental mercury with the help of intracellular thiols and NADPH as a cofactor (Schottel 1974; Summers and Silver 1978; Fox and Walsh 1982; Misra 1992). Our earlier studies have shown that growing cells of different mercury-resistant bacteria reduce Hg2+ compounds to Hg(O) (Ray et al. 1989; Pahan et al. 1990a; Gachhui et al. 1989). We have also shown the effect of thiol compounds and flavins on mercury-degrading enzyme activities in mercury-resistant bacteria (Pahan et al. 1990b). Here we report that resting cells of mercury-resistant bacteria survive in a buffer system for several hours, synthesize inducible mercury-degrading enzymes and volatilize mercury from a mercury-containing buffer system. We know of no information regarding studies of mercury-degrading enzymes in resting mercury-resistant bacterial cells.

title: Molecular characterization of a porcine Group A rotavirus strain with G12 genotype specificity
abstract: A porcine Group A rotavirus strain (RU172) was detected and molecularly characterized during a surveillance study conducted for rotavirus infection in a pig farm located in a suburban area of Kolkata City, India. The G12 genotype specificity of RU172 was revealed by PCR-based genotyping assays following addition of a G12 type-specific primer (designed in our laboratory to pick up G12 isolates from field samples) and was confirmed by sequence analysis of the VP7-encoding gene. The RU172 strain exhibited maximum VP7 identities of 93.6% to 94.5% with human G12 strains at the deduced amino acid level. In spite of its G12 genotype nature, RU172 appeared to be distinct from human G12 rotaviruses and, on phylogenetic analysis, formed a separate lineage with human G12 strains. Among the other gene segments analyzed, RU172 belonged to NSP4 genotype B, had a NSP5 and VP6 of porcine origin, and shared maximum VP4 identities with porcine P[7] rotaviruses (94.3%–95.4% at the deduced amino acid level). Therefore, to the best of our knowledge, this is the first report of detection of an animal rotavirus strain with G12 genotype specificity. Detection of strains like RU172 provides vital insights into the genomic diversity of Group A rotaviruses of man and animals.

title: A Role of CREB in BRCA1 Constitutive Promoter Activity and Aromatase Basal Expression
abstract: Aromatase is the rate-limiting enzyme in estrogen biosynthesis and a key target in breast cancer treatment. Its ovary-specific promoter, pII, is induced in response to protein kinase A (PKA) activation. It has been proposed that breast cancer susceptibility gene 1, BRCA1, is involved in negative regulation of aromatase pII activity. Surprisingly, inhibition of PKA pathway by inhibitor H89 elevates basal aromatase expression while abolishes cAMP-mediated aromatase induction in an ovarian granulosa cell line, KGN. In this report, we decipher the mechanism by which the PKA pathway negatively regulates aromatase basal expression. We show that PKA pathway plays a positive role in the expression of BRCA1. H89 effectively reduces endogenous BRCA1 mRNA levels as well as reporter gene expression from a BRCA1 promoter. Mutation of a cAMP-responsive element (CRE) in the BRCA1 promoter reduces BRCA1 expression. Chromatin immunoprecipitation (ChIP) shows that CRE-binding protein, CREB, binds to the BRCA1 promoter. Furthermore, knockdown of CREB in KGN cells leads to decreased BRCA1 level as well as elevated basal aromatase mRNA expression. These data demonstrate that both the CRE site in the BRCA1 promoter and CREB are required for BRCA1 constitutive expression. Our study suggests that PKA pathway exerts its negative impact on basal aromatase expression indirectly by contributing to the constitutive expression of BRCA1.

title: IKKbeta mediates cell shape-induced aromatase expression and estrogen biosynthesis in adipose stromal cells.
abstract: Aromatase (Cyp19) is a key enzyme in estrogen biosynthesis and an important target in breast cancer therapy. Within tumor microenvironment, tumor cells stimulate aromatase expression in adipose stromal cells (ASCs), which in turn promotes estrogen-dependent growth of estrogen receptor (ER)-positive tumor cells. However, it is not clear how aromatase transcription and estrogen biosynthesis are regulated in ASCs under a precancerous condition. Here we demonstrate that cell shape change alone is sufficient to induce aromatase expression in primary ASCs from cancer-free individuals. The activation of aromatase transcription is mediated by IkappaB kinase-beta (IKKbeta), a kinase previously known for its cancer-promoting activity in tumor cells. Activation of IKKbeta leads to elevated expression of transcription factor CCAAT/enhancer-binding protein-beta (C/EBPbeta), which binds to and stimulates two breast cancer-associated promoters of the aromatase gene. We also show that shape-induced estrogen production in ASCs can stimulate estrogen-dependent transcription in ER-positive breast tumor cells. We suggest that IKKbeta-dependent aromatase induction due to changes in cellular architecture in adipose tissue may contribute to the breast cancer risks associated with high mammagraphic density and obesity.

title: Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
abstract: In the neurogenic phase of CNS development, the proliferating progenitors are found medially within the neuroepithelium. The adherens junctions on the apical membrane of proliferating neural progenitors allow for cell–cell adhesion and medial stratification. In contrast, differentiating neuronal precursors delaminate and migrate laterally, establishing the laminar layers. Apical adherens junctions also establish the apical–basal polarity in neural progenitors, which in turn is postulated to lead to asymmetric inheritance of cell fate determinants during neurogenic divisions. The signaling pathways and cellular mechanisms that regulate the assembly and asymmetric localization of adherens junctions in neural progenitors remain elusive. Here we show that atypical PKCζ/λ (aPKCζ/λ) localizes at the apical membrane of proliferating neural stem cells, but not postmitotic neuronal precursors, in the developing chicken neural tube. This precise subcellular compartmentalization of the kinase activity provides an instructive signal for apical assembly of adherens junctions in a PI3K, Rac/Cdc42 signaling-dependent pathway. Apical aPKCζ coordinates neural stem cell proliferation and the overall stratification of cell types within the neural tube.