A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer.

Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, herein referred as DNA-PK) is a multifunctional kinase of high cancer relevance. DNA-PK is deregulated in multiple tumor types, including prostate cancer, and is associated with poor outcomes. DNA-PK was previously nominated as a therapeutic target and DNA-PK inhibitors are currently undergoing clinical investigation.

Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death.

EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition.

In response to DNA double-strand breaks, MAD2L2-containing shieldin complex plays a critical role in the choice between homologous recombination (HR) and non-homologous end-joining (NHEJ)-mediated repair. Here we show that EZH2 inhibition upregulates MAD2L2 and sensitizes HR-proficient epithelial ovarian cancer (EOC) to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner. CARM1 promotes MAD2L2 silencing by driving the switch from the SWI/SNF complex to EZH2 through methylating the BAF155 subunit of the SWI/SNF complex on the MAD2L2 promoter.

Structural and molecular strategy of photosynthetic apparatus organisation of wild flora halophytes.

Structural and molecular parameters of photosynthetic apparatus in plants with different strategies for the accumulation of salts were investigated. CO gas exchange rate, content of pigments, mesostructure, chloroplast ultrastructure and the biochemical composition of the membrane structural components in leaves were measured. The objects of the study were euhalophytes (Salicornia perennans, Suaeda salsa, Halocnemum strobilaceum), crynohalophyte (Limonium gmelinii), glycohalophyte (Artemisia santonica).

Mesophyll cell ultrastructure of wheat leaves etiolated by lead and selenium.

The ultrastructure of mesophyll cells was studied in leaves of the Triticum aestivum L. cv. "Trizo" seedlings after two weeks of growth on soil contaminated by Pb and/or Se.

An Essential Role for the Tumor-Suppressor Merlin in Regulating Fatty Acid Synthesis.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas, and meningiomas. Mutational inactivation of the gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that Nf2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1.

Targeting PAK1.

p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents.

Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type 1.

The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model.

Photochemical activity and the structure of chloroplasts in Arabidopsis thaliana L. mutants deficient in phytochrome A and B.

The reduced content of photoreceptors, such as phytochromes, can decrease the efficiency of photosynthesis and activity of the photosystem II (PSII). For the confirmation of this hypothesis, the effect of deficiency in both phytochromes (Phy) A and B (double mutant, DM) in 7-27-day-old Arabidopsis thaliana plants on the photosynthetic activity was studied in absence and presence of UV-A radiation as a stress factor. The DM with reduced content of apoproteins of PhyA and PhyB and wild type (WT) plants with were grown in white and red light (WL and RL, respectively) of high (130 μmol quanta m s) and low (40 μmol quanta m s) intensity.

Biochemistry and cell ultrastructure changes during senescence of Beta vulgaris L. leaf.

The comparative study of biochemical and ultrastructure features in senescing sugar beet (Beta vulgaris L.) leaves was carried out. One group of plants was grown under normal conditions in washed river sand and poured in turn with nitrate-containing mineral solution or water (N plants).

Effects of polyaromatic hydrocarbons on photosystem II activity in pea leaves.

The acute effects of three typical polyaromatic hydrocarbons (PAHs): naphthalene (Naph), phenanthrene (Phen) and fluoranthene (Flu) on photochemical activity of photosystem II (PSII) in detached leaves of 3-week-old pea plants were studied. The leaves were exposed in water with PAHs under white light for 0.5-72 h.

PAK signalling during the development and progression of cancer.

p21-Activated kinases (PAKs) are positioned at the nexus of several oncogenic signalling pathways. Overexpression or mutational activation of PAK isoforms frequently occurs in various human tumours, and recent data suggest that excessive PAK activity drives many of the cellular processes that are the hallmarks of cancer. In this Review, we discuss the mechanisms of PAK activation in cancer, the key substrates that mediate the developmental and oncogenic effects of this family of kinases, and how small-molecule inhibitors of these enzymes might be best developed and deployed for the treatment of cancer.

PKM2 enters the morpheein academy.

In this issue of Molecular Cell, Gao et al. (2012) show that the glycolytic enzyme PKM2, in its dimeric form, possesses protein kinase activity and phosphorylates STAT3 in the nucleus, thereby driving expression of genes that promote transformation.

Structural features of the salt glands of the leaf of Distichlis spicata 'Yensen 4a' (Poaceae).

The epidermal salt glands of the leaf of Distichlis spicata 'Yensen 4a' (Poaceae) have a direct contact with one or two water-storing parenchyma cells, which act as collecting cells. A vacuole occupying almost the whole volume of the collecting cell has a direct exit into the extracellular space (apoplast) through the invaginations of the parietal layer of the cytoplasm, which is interrupted in some areas so that the vacuolar-apoplastic continuum is separated only by a single thin membrane, which looks as a valve. On the basis of ultrastructural morphological data (two shapes of the extracellular channels, narrow and extended, are found in basal cells), the hypothesis on the mechanical nature of the salt pump in the basal cell of Distichlis leaf salt gland is proposed.

Characterization of the nature of photosynthetic recovery of wheat seedlings from short-term dark heat exposures and analysis of the mode of acclimation to different light intensities.

The nature of photosynthetic recovery was investigated in 10-d-old wheat (Triticum aestivum L., cv. Moskovskaya-35) seedlings exposed to temperatures of 40 and 42 degrees C for 20 min and to temperature 42 degrees C for 40 min in the dark.