Frazzled/Dcc acts independently of Netrin to promote germline survival during Drosophila oogenesis

ABSTRACT The Netrin receptor Frazzled/Dcc (Fra in Drosophila) functions in diverse tissue contexts to regulate cell migration, axon guidance and cell survival. Fra signals in response to Netrin to regulate the cytoskeleton and also acts independently of Netrin to directly regulate transcription during axon guidance in Drosophila. In other contexts, Dcc acts as a tumor suppressor by directly promoting apoptosis. In this study, we report that Fra is required in the Drosophila female germline for the progression of egg chambers through mid-oogenesis. Loss of Fra in the germline, but not the somatic cells of the ovary, results in the degeneration of egg chambers. Although a failure in nutrient sensing and disruptions in egg chamber polarity can result in degeneration at mid-oogenesis, these factors do not appear to be affected in fra germline mutants. However, similar to the degeneration that occurs in those contexts, the cell death effector Dcp-1 is activated in fra germline mutants. The function of Fra in the female germline is independent of Netrin and requires the transcriptional activation domain of Fra. In contrast to the role of Dcc in promoting cell death, our observations reveal a role for Fra in regulating germline survival by inhibiting apoptosis.

Vilyui-Markha interfluve of Yakutia: a region prospective for Cu-Ni-PGM mineralization

Materials are discussed on geologically similar structure of Norilsk ore district (NOD) and Vilyui-Markha interstream area (VMIA), which implies the latter prospects for Cu-Ni-PGM mineralization. Data is provided on Cu-Ni-Co-Zn mineral occurrences within Ygyattinsky diamondiferous region centered on VMIA. Geological similarities of NOD and VMIA are summarized below. Both regions are located in Mesozoic tectonomagmatic activation domain at the edge of large troughs: NOD is localized in the Siberian platform foredeep, and VMIA lies at Vilyui syneclise margin. NOD deposits are hosted by centroclines of large brachysynclines at slopes of Pyasinskoye dome. Within VMIA, prospects are located at Syuldyukarskoye dome slopes in margibal parts of large troughs. NOD and VMIA comprise Paleozoic marl-carbonate strata overlain by carbonaceous Carboniferous-Permian overburden, which could be assimilated by basaltic magma in Mesozoic contributing to its ore differentiation. Norilsk-Kharaelakh ore-bearing intrusion in VMIA appears to be similar to Kholomolokh sulfide-rich intrusion with its inferred extensive ore-bearing sills. They have similar composition and structure including presence of pegmatites. Ore-controlling Norilsk-Kharaelakh fault is believed to be simi- lar to Khatyryk-Kholomolokh fault, which was traced for 24 km by drilling and is one of sutures within deep-seated kimberlite-controlling Vilyui-Markha zone. This fault’s impact zone host concentrated geochemical anomalies and Cu-Ni-Co-Zn-Pt-Au-Ag Khomustakh occurrence. Based on this, Norilsk-type Cu-Ni prospects ranked as a potential ore cluster and three ore fields were identified

Jab1 (COPS5) as an Emerging Prognostic, Diagnostic and Therapeutic Biomarker for Human Cancer

Jab1 (C-Jun activation domain-binding protein-1) has been reported to be critically involved in regulating apoptosis, cell proliferation, cell cycle, thereby affecting numerous pathways, DDR (DNA damage response) regulation, and genomic instability. Jab1 (CSN5) dysregulation has been positively associated with oncogenesis via activating oncogenes and deactivating various tumor suppressors. Jab1 overexpression has been reported in several tumor forms, illuminating its potent efficacy in cancer progression and metastasis. Jab1 has instigated prompt research interest in elucidating inhibitors of numerous oncoproteins and oncogenes for chemotherapeutics. Our review has presented strong evidence for presenting the significance of Jab1 overexpression in numerous carcinomas and its involvement in modulating various signaling pathways for cancer cell survival. This review may project a new way for utilizing Jab1 as a strong target for developing potent inhibitory compounds targeting Jab1 that could be further utilized in chemoprevention with limited side effects. Altogether this review further confirmed the crucial involvement of Jab1 in carcinogenesis and tumorigenesis, displaying the strong potential of Jab1 as one of the potent cancer biomarkers.

TAL effectors with avirulence activity in African strains of Xanthomonas oryzae pv. oryzae

Background: Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a devastating disease of rice. Among the type-3 effectors secreted by Xanthomonas oryzae pv. oryzae to support pathogen virulence, the Transcription Activator-Like Effector (TALE) family plays a critical role. Some TALEs are major virulence factors that activate susceptibility (S) genes, overexpression of which contributes to disease development. Host incompatibility can result from TALE-induced expression of so-called executor (E) genes leading to a strong and rapid resistance response that blocks disease development. In that context, the TALE functions as an avirulence (Avr) factor. To date no such avirulence factors have been identified in African strains of Xanthomonas oryzae pv. oryzae. Results: With respect to the importance of TALEs in the Rice-Xoo pathosystem, we aimed at identifying those that may act as Avr factor within African Xoo. We screened 86 rice accessions, and identified 12 that were resistant to two African strains while being susceptible to a well-studied Asian strain. In a gain of function approach based on the introduction of each of the nine tal genes of the avirulent African strain MAI1 into the virulent Asian strain PXO99A, four were found to trigger resistance on specific rice accessions. Loss-of-function mutational analysis further demonstrated the avr activity of two of them, talD and talI, on the rice varieties IR64 and CT13432 respectively. Further analysis of TalI demonstrated the requirement of its activation domain for triggering resistance in CT13432. Resistance in 9 of the 12 rice accessions that were resistant against African Xoo specifically, including CT13432, could be suppressed or largely suppressed by trans-expression of the truncTALE tal2h, similarly to resistance conferred by the Xa1 gene which recognizes TALEs generally independently of their activation domain. Conclusion: We identified and characterized TalD and TalI as two African Xoo TALEs with avirulence activity on IR64 and CT13432 respectively. Resistance of CT13432 against African Xoo results from the combination of two mechanisms, one relying on the TalI-mediated induction of an unknown executor gene and the other on an Xa1-like gene or allele.

Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B

Photoactivated phytochrome B (PHYB) binds to antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to regulate hundreds of light responsive genes in Arabidopsis by promoting PIF degradation. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (AD) consisting of a hydrophobic activator motif flanked by acidic residues. A PIF3mAD mutant, in which the activator motif is replaced with alanines, fails to activate PIF3 target genes in Arabidopsis, validating the functions of the PIF3 AD in vivo. Intriguingly, the N-terminal photosensory module of PHYB binds immediately adjacent to the PIF3 AD to repress PIF3’s transactivation activity, demonstrating a novel PHYB signaling mechanism through direct interference of the transactivation activity of PIF3. Our findings indicate that PHYB, likely also PHYA, controls the stability and activity of PIFs via structurally separable dual signaling mechanisms.

Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B

Phytochrome B (PHYB) triggers diverse light responses in Arabidopsis by binding to a group of antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to promote PIF degradation, consequently downregulating PIF target genes. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (TAD) consisting of a sequence-specific, hydrophobic activator motif surrounded by acidic residues. A PIF3mTAD mutant in which the activator motif is replaced with alanines fails to activate PIF3 target genes in Arabidopsis in dark, light, and shade conditions, validating the in vivo functions of the PIF3 TAD. Intriguingly, binding of the N-terminal photosensory module of PHYB to the PHYB-binding site adjacent to the TAD inhibits its transactivation activity. These results unveil a photoresponsive transcriptional switching mechanism in which photoactivated PHYB directly masks the transactivation activity of PIF3. Our study also suggests the unexpected conservation of sequence-specific TADs between the animal and plant kingdoms.

Structural basis of phosphorylation kinetics in the transcriptional activation domain (TAD) of c-Jun and insight of two new phosphorylation sites Ser58 and Thr62

Protein phosphorylation is one of the most important posttranslational modifications observed on biomolecules. Nearly one-third of the cell cycle protein undergoes phosphorylation at some stage of the lifespan. Multi-site phosphorylation is well known in biological systems, including those in transcription factors. Multisite phosphorylation on transcription factors brings about their activation and/or inactivation. c-Jun is one of such transcription factors, whose function is dependent upon the state of phosphorylation. N-terminal phosphorylation required for c-Jun activity, while C-terminal one suppresses its activity. c-Jun contains a transcriptional activation domain (TAD) at N-terminus. It is known that four residues viz., Ser63, Ser73, Thr91 and Thr93 get phosphorylated which is required for its functional dimerization. However, there is no evidence if there exists any phosphorylation kinetics in c-Jun. In this paper, for the first time, it has been demonstrated that there exist phosphorylation kinetics within TAD. NMR based analysis suggested that Ser63 follows the fast kinetic while, Thr91 slow and Ser73 and Thr93 fall in the intermediate category. The four sites follow the following trend in their kinetics Ser63 > Ser73 > Thr93 > Thr91. Similar phosphorylation kinetics was also observed inside the C3H 10T0.5 fibroblast. NMR-based experiments also suggested the phosphorylation of two additional sites at Ser58 and Thr62. However, a detailed significance of these phosphorylation kinetic, as well as newly identified sites, is yet to be discovered.