Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26.

Human dual-specificity phosphatase 26 (DUSP26) is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C), the high-resolution structure of its catalytically active form has not been resolved.

Gender-specific metabolomic profiling of obesity in leptin-deficient ob/ob mice by 1H NMR spectroscopy.

Despite the numerous metabolic studies on obesity, gender bias in obesity has rarely been investigated. Here, we report the metabolomic analysis of obesity by using leptin-deficient ob/ob mice based on the gender. Metabolomic analyses of urine and serum from ob/ob mice compared with those from C57BL/6J lean mice, based on the (1)H NMR spectroscopy in combination with multivariate statistical analysis, revealed clear metabolic differences between obese and lean mice.

High-resolution crystal structure of the catalytic domain of human dual-specificity phosphatase 26.

Dual-specificity phosphatases (DUSPs) play an important role in regulating cellular signalling pathways governing cell growth, differentiation and apoptosis. Human DUSP26 inhibits the apoptosis of cancer cells by dephosphorylating substrates such as p38 and p53. High-resolution crystal structures of the DUSP26 catalytic domain (DUSP26-C) and its C152S mutant [DUSP26-C (C152S)] have been determined at 1.

Molecular mimicry-based repositioning of nutlin-3 to anti-apoptotic Bcl-2 family proteins.

The identification of off-target binding of drugs is a key to repositioning drugs to new therapeutic categories. Here we show the universal interactions of the p53 transactivation domain (p53TAD) with various anti-apoptotic Bcl-2 family proteins via a mouse double minute 2 (MDM2) binding motif, which play an important role in transcription-independent apoptotic pathways of p53. Interestingly, our structural studies reveal that the anti-apoptotic Bcl-2 family proteins and MDM2 share a similar mode of interaction with the p53TAD.

The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily.

Binding of the 4-1BB ligand (4-1BBL) to its receptor, 4-1BB, provides the T lymphocyte with co-stimulatory signals for survival, proliferation, and differentiation. Importantly, the 4-1BB-4-1BBL pathway is a well known target for anti-cancer immunotherapy. Here we present the 2.

The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-X(L)-binding motif.

While the transcription-dependent mechanism of p53 has been extensively studied, recently the transcription-independent apoptotic activity of p53 has also been described. Bcl-2 and Bcl-X(L) interact with p53 and induce apoptosis. Initially, the p53 DNA-binding domain (p53DBD) was found to bind to Bcl-2 and Bcl-X(L).

Waveform reliability with different recording electrode placement in facial electroneuronography.

Electroneuronography (ENoG) has become a useful test for estimating the degree of facial nerve degeneration and predicting the prognosis in patients with facial nerve palsy. Test results may be influenced by several factors, including the electrode positions, skin resistance, stimulus magnitude, and possible artifacts. Regarding recording electrode positions, different groups have used two different locations, the nasolabial fold and nasal ala.