Starvation Induces Proteasome Autophagy with Different Pathways for Core and Regulatory Particles

Citation: Waite, K. A., De-La Mota-Peynado, A., Vontz, G., & Roelofs, J. (2016). Starvation Induces Proteasome Autophagy with Different Pathways for Core and Regulatory Particles. Journal of Biological Chemistry, 291(7), 3239-3253. doi:10.1074/jbc.M115.699124The proteasome is responsible for the degradation of many cellular proteins. If and how this abundant and normally stable complex is degraded by cells is largely unknown. Here we show that in yeast, upon nitrogen starvation, proteasomes are targeted for vacuolar degradation through autophagy. Using GFP-tagged proteasome subunits, we observed that autophagy of a core particle (CP) subunit depends on the deubiquitinating enzyme Ubp3, although a regulatory particle (RP) subunit does not. Furthermore, upon blocking of autophagy, RP remained largely nuclear, although CP largely localized to the cytosol as well as granular structures within the cytosol. In all, our data reveal a regulated process for the removal of proteasomes upon nitrogen starvation. This process involves CP and RP dissociation, nuclear export, and independent vacuolar targeting of CP and RP. Thus, in addition to the well characterized transcriptional up-regulation of genes encoding proteasome subunits, cells are also capable of down-regulating cellular levels of proteasomes through proteaphagy

Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2

The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly understood. Here we report that the inducible nuclear dual-specificity MAP kinase phosphatase (MKP) DUSP2, a known regulator of the ERK and p38 MAPKs, is unique amongst the MKP family in being able to bind to both ERK3 and ERK4. This interaction is mediated by a conserved common docking (CD) domain within the carboxyl-terminal domains of ERK3 and ERK4 and the conserved kinase interaction motif (KIM) located within the non-catalytic amino terminus of DUSP2. This interaction is direct and results in the dephosphorylation of ERK3 and ERK4 and the stabilization of DUSP2. In the case of ERK4 its ability to stabilize DUSP2 requires its kinase activity. Finally, we demonstrate that expression of DUSP2 inhibits ERK3 and ERK4-mediated activation of its downstream substrate MK5. We conclude that the activity of DUSP2 is not restricted to the classical MAPK pathways and that DUSP2 can also regulate the atypical ERK3/4-MK5 signalling pathway in mammalian cells

Individual and combined soy isoflavones exert differential effects on metastatic cancer progression

To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein (GFP) tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg/kg body weight (BW) or a combination of genistein (10 mg/kg BW), daidzein (9 mg/kg BW), and glycitein (1 mg/kg BW) three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase (PI3-K) pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10/84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9/84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis

Application of Spectral Remote Sensing for Agronomic Decisions

Remote sensing has provided valuable insights into agronomic management over the past 40 yr. The contributions of individuals to remote sensing methods have lead to understanding of how leaf reflectance and leaf emittance changes in response to leaf thickness, species, canopy shape, leaf age, nutrient status, and water status. Leaf chlorophyll and the preferential absorption at different wavelengths provides the basis for utilizing reflectance with either broad-band radiometers typical of current satellite platforms or hyperspectral sensors that measure reflectance at narrow wavebands. Understanding of leaf reflectance has lead to various vegetative indices for crop canopies to quantify various agronomic parameters, e.g., leaf area, crop cover, biomass, crop type, nutrient status, and yield. Emittance from crop canopies is a measure of leaf temperature and infrared thermometers have fostered crop stress indices currently used to quantify water requirements. These tools are being developed as we learn how to use the information provided in reflectance and emittance measurements with a range of sensors. Remote sensing continues to evolve as a valuable agronomic tool that provides information to scientists, consultants, and producers about the status of their crops. This area is still relatively new compared with other agronomic fields; however, the information content is providing valuable insights into improved management decisions. This article details the current status of our understanding of how reflectance and emittance have been used to quantitatively assess agronomic parameters and some of the challenges facing future generations of scientists seeking to further advance remote sensing for agronomic applications

Model Lessons about Geography and Teaching with Primary Sources

Model Lessons for Teaching with Primary Sources to use with The Student Atlas of Oregon.https://pdxscholar.library.pdx.edu/geographyed_instructional/1004/thumbnail.jp