Luzp4 defines a new mRNA export pathway in cancer cells

Cancer testis antigens (CTAs) represented a poorly characterized group of proteins whose expression is normally restricted to testis but are frequently up-regulated in cancer cells. Here we show that one CTA, Luzp4, is an mRNA export adaptor. It associates with the TREX mRNA export complex subunit Uap56 and harbours a Uap56 binding motif, conserved in other mRNA export adaptors. Luzp4 binds the principal mRNA export receptor Nxf1, enhances its RNA binding activity and complements Alyref knockdown in vivo. Whilst Luzp4 is up-regulated in a range of tumours, it appears preferentially expressed in melanoma cells where it is required for growth

An evaluation of the effectiveness of protected areas in Thailand

Thailand is a biodiversity hotspot and home to over 1000 bird species, 15,000 plant species, and five of the World Wildlife Fund’s Global 200 Ecoregions of ecological significance. To preserve their unique ecosystems, the Thai government has established and maintained protected areas (PA) which in 2020, are estimated to cover 19% of Thailand’s land area. The success of these areas in preserving biodiversity to date is somewhat ambiguous. Using gap analyses, we evaluated the extent and adequacy of coverage provided by these PAs for the preservation of these unique ecoregions, to threatened amphibian, bird, and mammal species richness hotspots and at a range of altitudes within Thailand. Regionally, the Indochina dry forests, Northern Khorat Plateau moist deciduous forests and Malaysian Peninsula rainforests are all under-represented. Though opportunities exist for their protection through marine designation, mangrove and wetland ecosystems are also seriously under-represented in the current spatial layout and network connectivity of Thailand’s protected area system. Highland areas (>750 m elevation) are well-protected, in contrast to the lower altitude areas where human and agricultural pressures are higher. Hotspots of threatened birds located in the northern and southern regions of Thailand, as well as most of the central threatened mammal hotspot, are inadequately covered (<10%). The current PAs could be expanded with a focus on these key areas, or further PAs created to address these gaps in provision. The Thai PA network is also highly fragmented and, in addition to increasing the area covered, contiguity and connectivity of the network should be considered. With human population expansion in the central lowland area particularly, there will be challenges and trade-offs to be negotiated along with enforcement within existing areas. We hope, though, that the results of this study can aid policymakers in improving Thai conservation effectiveness

A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility

CXCL12 governs cellular motility, a process deregulated by hematopoietic stem cell oncogenes such as p210-BCR-ABL. A phosphoproteomics approach to the analysis of a hematopoietic progenitor cell line treated with CXCL12 and the Rac 1 and 2 inhibitor NSC23766 has been employed to objectively discover novel mechanisms for regulation of stem cells in normal and malignant hematopoiesis. The proteomic data sets identified new aspects of CXCL12-mediated signaling and novel features of stem cell regulation. We also identified a novel phosphorylation event in hematopoietic progenitor cells that correlated with motile response and governed by the chemotactic factor CXCL12. The novel phosphorylation site on PTPRC/CD45; a protein tyrosine phosphatase, was validated by raising an antibody to the site and also using a mass spectrometry absolute quantification strategy. Site directed mutagenesis and inhibitor studies demonstrated that this single phosphorylation site governs hematopoietic progenitor cell and lymphoid cell motility, lies downstream from Rac proteins and potentiates Src signaling. We have also demonstrated that PTPRC/CD45 is down-regulated in leukemogenic tyrosine kinase expressing cells. The use of discovery proteomics has enabled further understanding of the regulation of PTPRC/CD45 and its important role in cellular motility in progenitor cells