Cutaneous HPV23 E6 Prevents p53 Phosphorylation through Interaction with HIPK2

Ultraviolet irradiation (UV) is the major risk factor for the development of skin cancer. Moreover, increasing evidence suggests cutaneotropic human papillomaviruses (HPV) from the beta genus to play a causal role as a co-factor in the development of cutaneous squamous cell carcinoma. Homeodomain-interacting protein kinase 2 (HIPK2) operates as a potential suppressor in skin tumorigenesis and is stabilized by UV-damage. HIPK2 is an important regulator of apoptosis, which forms a complex with the tumor suppressor p53, mediating p53 phosphorylation at Ser 46 and thus promoting pro-apoptotic gene expression. In our study, we demonstrate that cutaneous HPV23 E6 protein directly targets HIPK2 function. Accordingly, HPV23 E6 interacts with HIPK2 both in vitro and in vivo. Furthermore, upon massive UVB-damage HPV23 E6 co-localizes with endogenous HIPK2 at nuclear bodies. Functionally, we demonstrate that HPV23 E6 inhibits HIPK2-mediated p53 Ser 46 phosphorylation through enforcing dissociation of the HIPK2/p53 complex. In addition, HPV23 E6 co-accumulates with endogenous HIPK2 upon UV damage suggesting a mechanism by which HPV23 E6 keeps HIPK2 in check after UV damage. Thus, cutaneous HPV23 E6 prevents HIPK2-mediated p53 Ser 46 phosphorylation, which may favour survival of UV-damaged keratinocytes and skin carcinogenesis by apoptosis evasion

Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities

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Atropodiastereoselective C-H Olefination of Biphenyl p-Tolyl Sulfoxides with Acrylates

A stereoselective method for the synthesis of axially chiral biaryl scaffolds by C-H bond functionalization was accomplished using chiral sulfoxide both as the directing group enabling the regioselective activation of a C-H bond and as the chiral auxiliary generating an asym. environment in the coordination sphere of the metal complex. We have demonstrated the directing ability of the p-tolylsulfinyl group in promoting the Pd(II)-catalyzed C-H olefination of biphenyls. Thus, reacting biphenyl p-tolyl sulfoxide I (R = H) as a mixt. of atropisomers with Me acrylate in the presence of Pd(OAc)2 gave coupling product I [R = (E)-CH:CHCO2Me] in 87% yield (4.6:1 d.r. SaR:SaS)

Palladium-Catalyzed Intramolecular Direct Arylation of 2-Bromo-diaryl Sulfoxides via C-H Bond Activation

Efficient access to dibenzothiophene-S-oxides, e.g., I, from differently substituted 2-bromo-diarylsulfinyl moieties using ligandless Pd(OAc)2 as the catalyst and KOAc as the base in dimethylacetamide at 130 °C is reported. Various dibenzothiophene-S-oxides were obtained in excellent yields

Swift heavy ion irradiation of crystalline CdTe

The influence of high electronic energy deposition in cadmium telluride (CdTe) was investigated using Rutherford backscattering spectrometry in channelling configuration as well as high-resolution transmission electron microscopy. Swift heavy ion irradiation was performed at room temperature with 185 MeV Au ions at perpendicular and non-perpendicular ion incidence. Independent of the ion incidence angle, neither ion beam induced point defects nor amorphous ion tracks were observed along the ion path. In contrast, the irradiated layer possesses a high crystalline quality even after irradiation with high ion fluences, i.e. multiple ion overlap. Nevertheless, irradiation with swift heavy ions leads to the formation of extended defects in a thin layer close to the sample surface. With increasing ion fluence the concentration of these extended defects increases continuously. This suggests that high electronic energy deposition causes the formation of defects, however, the combination of the high defect mobility within the thermal spike and the high ionicity of CdTe may benefit an effective recovery of the ionic bonds and consequently an easy recovery of the lattice, i.e. a nearly perfect recrystallization. The experimentally observed high defect resistivity enables a high doping of foreign atoms in CdTe over a wide depth range without the formation of lattice defects which is important for the use of CdTe as an effective absorber for solar cells

Palladium-Catalyzed Intramolecular Direct Arylation of 2‑Bromo-diaryl Sulfoxides via C–H Bond Activation

Efficient access to dibenzothiophene-<i>S</i>-oxides from differently substituted 2-bromo-diarylsulfinyl moieties using ligandless Pd(OAc)₂ as the catalyst and KOAc as the base in dimethylacetamide at 130 °C is reported. Various dibenzothiophene-<i>S</i>-oxides were obtained in excellent yields