Podcasts about mst2

This month on the Sounds of midnight riot we have host Jaegerossa up in hour 1 playing a high energy blend of disco and house that will get you bouncing! Then in hour 2 we welcome DJ Emma to the show with a super Disco Mix! Enjoy!Jaegerossa Hour1:TSOMR POD DEC/NOV1.  Jaegerossa - days trying MST2.  GROOVEMASTA party fever master3.  Black Riot 138 DAISUKE MIYAMOTO4.  Lux Experience - Celebrate5.  Sammy Deuce -  24Bit MASTER6.  Sonic Soul Orch Ft Kathy Brown - Risk Assement Mix "Good Inside"(RA Remix) RM MAS7.  Dominic Dawson feat ROY INC & Miotina 'We Want The Funk' Yam Who_ remix_MST8.  Young Pulse (ft. Fleur De Mur) - Smooth Sweet Talker (Main Mix) [MASTER 20230922]9.  Do You Wanna (Daphni Edit)Donnell Pitman ft. DaphniDo You Wanna - Daphni (Caribou) Edit 12"10. SYLVESTER - Dance Disco Heat [The Reflex Revision] 11. Roberta KellyRoberta Kelly - My Sweet Lord (Young Pulse retouch)12. DEVINE WHO - JAEGEROSSA REMIX MSTDJ Emma:1. There's a Better Place – Crazy P2. Kaleidoscopic Planet – The Illustrious Blacks3. La Chatte Au Baron – Art Of Tones & Chatobaron4. New Jersey Deep – Black Science Orchestra5. Runaround (Tee's 12”Mix) – Martha Wash6. Angels (Crackazat remix) – House Gospel Choir, Morgan (UK)7. Off You Go (Young Pulse Remix) – Wayata, Astrid James, Young Pulse8. I Need A Freak (Young Pulse Edit)9. Holy Spirit ( DJ Mark Brickman Remix) – Platinum City10. Runnin (Dr. Packer Remix) – Mistura, Dr. Packer11. All Night Long – Alexis P Suter12. Out Of Your Mind (ft. Confidence Man) – CC Disco13. Freak It – DJ Mark Brickman14. He Loves Me 2 (Silk's 12”) – CeCe Peniston

Volume 11, Issue 25 of @Oncotarget reported that to examine the role of RSK in AML, the authors analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in Acute Myeloid Leukemia cell lines and patient Acute Myeloid Leukemia cells. Therefore, the authors investigated whether BI-D1870 potentiates the anti-leukemic activity of vincristine by targeting mitotic exit. Combination treatment of BI-D1870 and vincristine synergistically increased mitotic arrest and apoptosis in acute leukemia cells. These data show that BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit, providing a novel approach to overcoming vincristine resistance in AML cells. Dr. Kathleen M. Sakamoto from Stanford University School of Medicine said, "Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematologic malignancy characterized by the accumulation of immature myeloid blasts with resultant peripheral blood cytopenia." Treatment of cells with microtubule targeting agents, including paclitaxel and the vinca alkaloid vincristine, blocks the proper formation of the mitotic spindle through inhibition of microtubule dynamics, resulting in the prolonged mitotic arrest of cancer cells. MTAs-treated mitotic arrested cells may undergo apoptosis in mitosis, however, the rapid degradation of Cyclin B due to an insufficient SAC leads to the mitotic slippage into tetraploid G1 stage in resistant cells. Though vinca alkaloid microtubule-destabilizing compounds have shown clinical efficacy against various hematological malignancies and were included in combination chemotherapy of the VAPA study, they are not currently used in induction chemotherapy for AML due to their high toxicity against lymphoid cells and rapid degradation by myeloperoxidase in AML cells. In this study, they demonstrate that BI-D1870, a potent inhibitor of RSK, induces mitotic arrest, and apoptosis in AML cells without inhibiting CDC2 and CDC25C. Furthermore, BI-D1870 synergizes with vinca alkaloid vincristine in AML cells, suggesting that inhibition of mitotic exit with BI-D1870 could be a promising novel approach for AML therapy in combination with MTAs. The Sakamoto Research Team concluded in their Oncotarget Research Paper that BI-D1870 is a reversible pan-RSK inhibitor, showing > 500-fold higher activity for RSK than other AGC kinases. BI-D1870 also inhibits the activity of PLK1, Aurora-B, MELK, PIM3, MST2, and GSK3β at higher concentrations than for RSK. BI-D1870 and BRD7389 have been reported to inhibit proliferation and significantly increase the G2/M population in melanoma cells. BI-D1870 does not have proper physicochemical properties for clinical application. Future structure-activity relationships study for BI-D1870 is required to improve solubility and pharmacokinetic profiles for in vivo preclinical and clinical studies. Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27630 Full text - https://www.oncotarget.com/article/27630/text/ Correspondence to - Kathleen M. Sakamoto - kmsakamo@stanford.edu Keywords - acute myeloid leukemia, BI-D1870, RSK, vincristine, spindle assembly checkpoint About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105

Fengyuan Tang has demonstrated that the kinases NDR1 and NDR2 mediate Hippo signaling during thymocyte migration.

Mitosis is the process by which sister chromatids are equally segregated into two daughter cells. Tight control in various events during mitotic progression is essential for maintaining chromosome stability. Mitotic kinases including Cyclin dependent kinase 1 (Cdk1) and Aurora family are required for regulating proper mitotic progression by phosphorylating mitotic substrates thereby, controlling their activities, localization or abundance. On the other hand, these mitotic kinases are modulated by de-novo synthesis, activators, phosphorylation and ubiquitin-dependent proteolysis. A thorough understanding of the function and regulation of mitotic kinases could further our knowledge on mitotic progression. In the first part of the thesis, we investigated the expression, localization and regulation of human Lats1 kinase, which is a close homologue of the yeast Dbf2 kinase family involved in the mitotic exit network (MEN). Despite the fact that Lats1 has been suggested to be a spindle protein that binds and inactivates Cdk1, we found that Lats1 is mainly cytoplasmic throughout the cell cycle by immunofluorescence microscopy. Both yeast two-hybrid and coimmunoprecipitation showed no significant interaction between Lats1 and Cdk1. Although Lats1 was highly phosphorylated during mitosis, no detectable kinase activity was observed. However, we identified Ste20 like kinase MST2 as the upstream regulator of human Lats1. Phosphorylation of Lats1 by Mst2 resulted in the activation of Lats1 kinase activity both in vivo and in vitro. This kinase-substrate relation was proven to be specific, as another distant Mst2 homolog, Mst4, did not possess this ability. Subsequent mass-spectrometry-based phosphosites analysis revealed that Mst2 phosphorylates Lats1 on more than five residues. Alanine mutations on Lats1T1079 and S909 impaired Lats1 kinase activity. Thus, we could not confirm the suggested role of Lat1 in mitosis. Instead, we show that similar to its Drosophila ortholog, Lats1 is involved in the Mst2 signaling pathway and might control developmentally regulated cell proliferation and apoptosis in mammals. In the second part of this thesis, we characterized hBora, a novel Aurora A interactor originally found in Drosophila. We show that hBora is upregulated and phosphorylated during mitosis. siRNA-mediated knockdown of hBora led to spindle formation defects and aneuploidy. hBora overexpression caused monoastral spindle formation and mislocalization not only of Aurora A but also Plk1. Further investigations showed that Cdk1 phosphorylation on hBoraSer252 leads to Plk1 binding and this may promote the SCF-mediated proteolysis of hBora. Indeed, Plk1 depletion led to an increase in hBora levels. Interestingly, the co-depletion of both hBora and Plk1 (to lower hBora levels in Plk1 depleted cells) rescued the localization of Aurora A to the centrosomes and bipolar spindle formation. Thus, we propose that hBora is a functional link between Plk1 and Aurora A and that by modulating the proteolysis of hBora, Plk1 could regulate Aurora A localization and activity. At the end, we also investigated the function of Aurora A and could show that Aurora A is required for centriole cohesion and centrosome separation.

The major goal of the project was the investigation of proteins that regulate dynamic rearrangements of the actin cytoskeleton in Dictyostelium discoideum amoebae. Among the proteins studied in detail were (i) D. discoideum vasodilator stimulated phosphoprotein DdVASP and a new profilin isoform as putative regulators of filopodia formation, and (ii) the Ste20-like kinases Krs1 and Severin-Kinase as members of signalling cascades towards the actin cytoskeleton. Filopodia are bundles of actin filaments projecting from the cell surface. They are found on a variety of cell types and are needed among others, for cell adhesion, sensory and exploratory functions. Filopodia are frequently found associated with sheet-like arrays of actin filaments called lamellipodia and membrane ruffles. The function of the VASP homolog from D. discoideum in filopodia formation was studied using molecular, biochemical and cell biological approaches. The protein sequence of DdVASP shares a significant homology to the members from other species. The protein harbours two Ena/VASP homology domains EVH1 and EVH2 separated by a polyproline stretch. The EVH2 domain is characterised by a G-actin binding site (GAB), an F-actin binding site (FAB) and a tetramerisation domain. As a tetramer the DdVASP protein can nucleate actin polymerization and bundle actin filaments. The in vitro nucleating activity of DdVASP is salt dependent and its nucleating activity is completely abolished at 100 mM salt. However, the F-actin bundling activity as determined by the low speed sedimentation assay was not disturbed. The ability of DdVASP to influence the binding of capping protein to the growing ends of the actin filaments was tested through elongation of capped F-actin seeds and by depolymerization of capped filaments upon dilution below the critical concentration of the barbed ends. Results from both sets of experiments showed that DdVASP cannot remove capping protein from the barbed ends. The D. discoideum formin dDia2, which was previously reported to be essential for filopodia formation could elongate the capped F-actin seeds. In vitro biochemical data led to the conclusion that the bundling activity of DdVASP is the essential in vivo function to stabilise actin filaments in emerging filopodia. To test this hypothesis, a DdVASP null mutant was isolated. As expected the mutant failed to produce any filopodia. Expression of wild type DdVASP, but not DdVASPFAB, rescued the phenotype suggesting the importance of the bundling activity of DdVASP in filopodia formation. To confirm that the data obtained with DdVASP were not species specific, key biochemical functions of HsVASP were also tested. The results indicated that VASPs are functionally well conserved throughout evolution. During this study, a third profilin isoform, profilin III, was further characterised. Specific interaction between profilin III and DdVASP was discovered. Profilin III shares a limited homology at the amino acid level with the other two and well studied profilins. Polyclonal antibodies that recognise only the profilin III isoform showed that in wild type cells profilin III represents less than 1% of all profilins. This suggests a distinct role for profilin III, because a low protein concentration argues against an actin sequestering function. Immunolocalisation studies showed profilin III in filopodia and enriched at their tips. Cells lacking the profilin III protein show defects in cell motility during chemotaxis. The second part of the project dealt with the characterisation of two D. discoideum Germinal Centre Kinases (GCK). The catalytic domain of Krs1 was found to be highly homologous to the catalytic region of human MST1 and MST2 from the GCK-II subfamily. The regulatory region harbours the putative inhibitory domain (aa 330-379) and a possible multimerization (SARAH) domain (aa 412-458) described for GCKs in higher organisms. This SARAH region spans about 50 amino acid residues, is located at the extreme carboxyl terminus and most likely forms an  - helical coiled-coil motif. GFP-Krs1 overexpressing wild type cells showed an enrichment of the kinase in the cell cortex, and motility of these cells during aggregation was reduced. Krs1 knockout strains exhibited only subtle differences to wild type cells. Severin kinase is encoded by the gene svkA, and phylogenetic analysis groups it into subfamily GCK-III, along with human MST3, MST4 and YSK/SOK-1. Immunoblot analysis with polyclonal antibodies showed an uniform expression level throughout development. Gene disruption of svkA resulted in cells that had problems to divide both in submerged or in shaking cultures. Though the motility and chemotaxis of these cells remain unaltered compared to the wild type cells, the movement of the multicellular slugs is disturbed. In addition, development was delayed and the mutant formed aberrant fruiting bodies.