IKK(α) controls canonical TGF(ß)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells.

The epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ-SMAD signaling pathway is an inductor of EMT in many tumor types. One hallmark of EMT is downregulation of the adherens junction protein E-cadherin, a process mediated by transcription factors such as the zinc fingers SNAIL and SLUG. Here, we report that the catalytic IκB kinase (IKK) subunit IKKα is necessary for the silencing of E-cadherin in a Panc1 cell model of TGFβ-SMAD-mediated EMT, independently of NFκB.

Molecular framework of steroid/retinoid discrimination in 17beta-hydroxysteroid dehydrogenase type 1 and photoreceptor-associated retinol dehydrogenase.

Steroids and retinoids are signaling molecules that control a variety of physiological processes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the reduction of estrone to estradiol, supplying biologically active estrogen-regulating sex-specific differentiation. Photoreceptor-associated retinol dehydrogenase (prRDH) is evolutionarily closely related to 17beta-HSD1 but reduces all-trans retinal to all-trans retinol, contributing to rhodopsin regeneration in the visual cycle.

In search for function of two human orphan SDR enzymes: hydroxysteroid dehydrogenase like 2 (HSDL2) and short-chain dehydrogenase/reductase-orphan (SDR-O).

The protein superfamily of short-chain dehydrogenases/reductases (SDRs) today comprises over 20,000 members found in pro- and eukaryotes. Despite low amino acid sequence identity (only 15-30%), they share several similar characteristics in conformational structures, the N-terminal cofactor (NAD(P)/NAD(P)H) binding region being the most conserved. The enzymes catalyze oxido-reductive reactions and have a broad spectrum of substrates.

Human and zebrafish hydroxysteroid dehydrogenase like 1 (HSDL1) proteins are inactive enzymes but conserved among species.

Hydroxysteroid dehydrogenase like 1 protein (HSDL1) is an uncharacterized member of short-chain dehydrogenase/reductase (SDR) protein family. In search for functional assignment of both human and zebrafish HSDL1 we characterized the subcellular localization as well as the tissue distribution and performed a screen for putative substrates of HSDL1 enzymes. Surprisingly, human HSDL1 shows exchange of an amino acid in the active center (Sx(12)FSxxK instead of Sx(12)YSxxK) that is considered critical for catalysis.

Steroid metabolism in cnidarians: insights from Nematostella vectensis.

Cnidarians occupy a key evolutionary position as a sister group to bilaterian animals. While cnidarians contain a diverse complement of steroids, sterols, and other lipid metabolites, relatively little is known of the endogenous steroid metabolism or function in cnidarian tissues. Incubations of cnidarian tissues with steroid substrates have indicated the presence of steroid metabolizing enzymes, particularly enzymes with 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity.

Deletion of exon 8 increases cisplatin-induced E-cadherin cleavage.

E-Cadherin-mediated cell-cell adhesion plays a key role in epithelial cell survival and loss of E-cadherin or beta-catenin expression is associated with invasive tumor growth. Somatic E-cadherin mutations have been identified in sporadic diffuse-type gastric carcinoma. Here, we analysed the fate of E-cadherin with an in frame deletion of exon 8 compared to wild-type E-cadherin and the involved signalling events during cisplatin-induced apoptosis.