Biology Commons^™

Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis And Is Traceable In The Circulating Extracellular Vesicles, Anabarasu Kannan, Julie V. Philley, Kate L. Hertweck, Harrison Ndetan, Karan P. Singh, Subramaniam Sivakumar, Robert B. Wells, Ratna K. Vadlamudi, Santanu Dasgupta

Biology Faculty Publications and Presentations

Triple negative breast cancer (TNBC) has poor survival, exhibits rapid metastases, lacks targeted therapies and reliable prognostic markers. Here, we examined metastasis promoting role of cancer testis antigen SPANXB1 in TNBC and its utility as a therapeutic target and prognostic biomarker. Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles (sEVs). cDNA microarray analysis of TNBC cells stably integrated with a metastasis suppressor SH3GL2 identifed SPANXB1 as a potential target gene. TNBC cells overexpressing SH3GL2 exhibited decreased levels of both SPANXB1 mRNA and protein. Silencing of SPANXB1 reduced migration, invasion …

Engineering Dna Recognition And Allosteric Response Properties Of Tetr Family Proteins By Using A Module-Swapping Strategy, Rey P. Dimas, Benjamin R. Jordan, Xian-Li Jiang, Catherine Martini, Joseph S. Glavy, Dustin P. Patterson, Faruck Morcos, Clement T.Y. Chan

Biology Faculty Publications and Presentations

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and …

A Csra-Binding, Trans-Acting Srna Of Coxiella Burnetii Is Necessary For Optimal Intracellular Growth And Vacuole Formation During Early Infection Of Host Cells, Shaun Wachter, Matteo Bonazzi,, Kyle Shifflett, Abraham Moses, Rahul Raghavan, Michael F. Minnick

Biology Faculty Publications and Presentations

Coxiella burnetii is an obligate intracellular gammaproteobacterium and zoonotic agent of Q fever. We previously identified 15 small non-coding RNAs (sRNAs) of C. burnetii. One of them, CbsR12 (Coxiella b urnetii small RNA 12), is highly transcribed during axenic growth and becomes more prominent during infection of cultured mammalian cells. Secondary structure predictions of CbsR12 revealed four putative CsrA-binding sites in stem loops with consensus AGGA/ANGGA motifs. We subsequently determined that CbsR12 binds to recombinant C. burnetii CsrA-2, but not CsrA-1, proteins in vitro. Moreover, through a combination of in vitro and cell …

Correcting Forensic Dna Errors, Greg Hampikian

Biology Faculty Publications and Presentations

DNA mixture interpretation can produce opposing conclusions by qualified forensic analysts, even within the same laboratory. The long-delayed publication of the National Institutes of Standards and Technology (NIST) study of 109 North American crime laboratories in this journal demonstrates this most clearly. This latest study supports earlier work that shows common methods such as the Combined Probability of Inclusion (CPI) have wrongly included innocent people as contributors to DNA mixtures.The 2016 President’s Council of Advisors on Science and Technology report concluded,“In summary, the interpretation of complex DNA mixtures with the CPI statistic has been an inadequately specified—and thus inappropriately subjective—method. …

How To Make A Weed: The Saga Of The Slender False Brome Invasion In The North American West And Lessons For The Future, Mitchell B. Cruzan

Biology Faculty Publications and Presentations

Historical herbarium collections and genetic analyses indicate that slender false brome (Brachypodium sylvaticum) was first introduced in test gardens in Oregon in the early 1900 s as part of the USDA’s plant introduction program. A small number of naturalized populations were established, but it was not until several decades later that this alien species became an aggressive invader. The Oregon invasive strains of false brome were generated as a consequence of mating among genetically divergent lineages. The resulting hybrid populations contained high levels of genetic variation that fueled the evolution of specific adaptations to the Pacific Northwest climate and ultimately …

Complex History Of Codiversification And Host Switching Of A Newfound Soricid-Borne Orthohantavirus In North America, Schuyler W. Liphardt, Hae Ji Kang, Laurie J. Dizney, Luis A. Ruedas, Joseph A. Cook, Richard Yanagihara

Biology Faculty Publications and Presentations

Orthohantaviruses are tightly linked to the ecology and evolutionary history of their mammalian hosts. We hypothesized that in regions with dramatic climate shifts throughout the Quaternary, orthohantavirus diversity and evolution are shaped by dynamic host responses to environmental change through processes such as host isolation, host switching, and reassortment. Jemez Springs virus (JMSV), an orthohantavirus harbored by the dusky shrew (Sorex monticola) and five close relatives distributed widely in western North America, was used to test this hypothesis. Total RNAs, extracted from liver or lung tissue from 164 shrews collected from western North America during 1983–2007, were analyzed for orthohantavirus …

Dietary Plasticity In A Specialist Predator, The Gyrfalcon (Falco Rusticolus): New Insights Into Diet During Brood Rearing, Bryce W. Robinson, Travis L. Booms, Marc J. Bechard, David L. Anderson

Biology Faculty Publications and Presentations

Climate and landscape change are expected to affect species’ distributions and interactions, with potentially harmful consequences for specialist predators. Availability of optimal prey can affect reproductive success in raptors, especially in the Arctic, where dramatic differences in prey availability occur both within and between years. However, behavioral responses of dietary specialist, resident predators such as Gyrfalcons (Falco rusticolus) to changes in prey availability remain poorly understood. To improve understanding of how climate-driven changes in prey availability may affect diet of avian predators in the Arctic, we characterized Gyrfalcon diet on the Seward Peninsula, Alaska, in 2014 and 2015 …

Antioxidant Capacity And Anoxia-Tolerance In Austrofundulus Limnaeus Embryos, Josiah Tad Wagner, Michael J. Knapp, Jason E. Podrabsky

Biology Faculty Publications and Presentations

Embryos of Austrofundulus limnaeus can tolerate extreme environmental stresses by entering into a state of metabolic and developmental arrest known as diapause. Oxidative stress is ubiquitous in aerobic organisms and the unique biology and ecology of A. limnaeus likely results in frequent and repeated exposures to oxidative stress during development. Antioxidant capacity of A. limnaeus was explored during development by measuring antioxidant capacity due to small molecules and several enzymatic antioxidant systems. Diapause II embryos can survive for several days in 1% hydrogen peroxide without indications of negative effects. Surprisingly, both small and large molecule antioxidant systems are highest during …

Genotype Network Intersections Promote Evolutionary Innovation, Devin P. Bendixsen, James Collet, Bjørn Østman, Eric J. Hayden

Biology Faculty Publications and Presentations

Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms of innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks—the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. However, the experimental characterization of genotype networks has been hindered by the vast number of genetic variants that need to be functionally analyzed. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We …

Evolution Of The Caribbean Species Of Columnea (Gesneriaceae) With An Emphasis On The Jamaican Species, James F. Smith, Maggie T.-Y. Ooi, Lacie J. Schulte, Keron C. St.E. Campbell, Judeen Meikle, John L. Clark

Biology Faculty Publications and Presentations

Premise of research. Biogeography has improved understanding of evolution and diversification of organisms on both continental and island systems. One complicated island group in terms of geological history and biogeographic pattern is the Caribbean island system. A comparison across taxonomic groups does not result in overarching patterns for this group of islands. Columnea has the greatest number of species endemic to the Caribbean for any genus in Gesneriaceae that is not mostly endemic to the Caribbean with 16 species. Thirteen of these species are found on Jamaica, the remaining three each endemic to Cuba, Hispaniola, and Puerto Rico. In …

A Framework To Guide Undergraduate Education In Interdisciplinary Science, Brie Tripp, Erin E. Shortlidge

Biology Faculty Publications and Presentations

An expanded investment in interdisciplinary research has prompted greater demands to integrate knowledge across disciplinary boundaries. Vision and Change similarly made interdisciplinary expectations a key competency for undergraduate biology majors; however, we are not yet synchronized on the meaning of interdisciplinarity, making this benchmark difficult to meet and assess. Here, we discuss aspects of interdisciplinarity through a historical lens and address various institutional barriers to interdisciplinary work. In an effort to forge a unified path forward, we provide a working definition of interdisciplinary science derived from both the perspectives of science faculty members and scientific organizations. We leveraged the existing …

Differences Between Male And Female Elite Free-Style Wrestlers In The Effects Of “Set Up” On Leg Attack, Sho Ito, Larry Crawshaw, Kazuyuki Kanosue

Biology Faculty Publications and Presentations

Leg attack is the most basic skill in free-style wrestling. Before executing a leg attack, balance and anticipation of the opponent must be disrupted. We defined this action as the “set up”. The aim of this study is knowledge about the effects of “set up” on the success rate of leg attacks, and answer to question: whether or not a gender difference exists in the use and effectiveness of “set ups” in the elite level of the wrestling matches. Material and Methods: We analyzed video recordings of 57 matches of male free-style wrestling seniors, 58 matches of female seniors, 60 …

Reduced-Impact Logging For Climate Change Mitigation (Ril-C) Can Halve Selective Logging Emissions From Tropical Forests, Anand Roopsind

Biology Faculty Publications and Presentations

Selective logging causes at least half of the emissions from tropical forest degradation. Reduced-impact logging for climate (RIL-C) is proposed as a way to maintain timber production while minimizing forest damage. Here we synthesize data from 61 coordinated field-based surveys of logging impacts in seven countries across the tropics. We estimate that tropical selective logging emitted 834 Tg CO₂ in 2015, 6% of total tropical greenhouse gas emissions. Felling, hauling, and skidding caused 59%, 31%, and 10% of these emissions, respectively. We suggest that RIL-C incentive programs consider a feasible target carbon impact factor of 2.3 Mg emitted per …

Rapid Habituation Of A Touch-Induced Escape Response In Zebrafish (Danio Rerio) Larvae, Adam C. Roberts, Julia Chornak, Joseph B. Alzagatiti, Duy T. Ly

Biology Faculty Publications and Presentations

Zebrafish larvae have several biological features that make them useful for cellular investigations of the mechanisms underlying learning and memory. Of particular interest in this regard is a rapid escape, or startle, reflex possessed by zebrafish larvae; this reflex, the Cstart, is mediated by a relatively simple neuronal circuit and exhibits habituation, a non-associative form of learning. Here we demonstrate a rapid form of habituation of the C-start to touch that resembles the previously reported rapid habituation induced by auditory or vibrational stimuli. We also show that touch-induced habituation exhibits input specificity. This work sets the stage for in vivo …

Engineering Repressors With Coevolutionary Cues Facilitates Toggle Switches With A Master Reset, Rey P. Dimas, Xian-Li Jiang, Jose Alberto De La Paz, Faruck Morcos, Clement T.Y. Chan

Biology Faculty Publications and Presentations

Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF …

Morpho-Molecular Characterization Of The Litostomatean Predatory Ciliate Phialina Pupula (Müller, 1773) Foissner, 1983 (Haptoria, Lacrymariidae), Ľubomír Rajter, William Bourland, Peter Vďačný

Biology Faculty Publications and Presentations

The morphology and phylogenetic position of a haptorian ciliate, Phialina pupula (Müller, 1773) Foissner, 1983, isolated from microaerobic sandy sediments of the floodplain area of the Boise River, Idaho, U.S.A., were studied using live observation, protargol impregnation, scanning electron microscopy, and the 18S rRNA gene as well as the ITS region. The Boise population of P. pupula is characterized by a size of about 60–130 × 20–50 μm, an elliptical macronucleus with a single micronucleus, highly refractive dumbbell-shaped inclusions scattered throughout the cytoplasm and concentrated in the anterior body half, a single subterminal/terminal contractile vacuole, about 10 μm long rod-shaped …

Co-Expression Of Vegf And Il-6 Family Cytokines Is Associated With Decreased Survival In Her2 Negative Breast Cancer Patients: Subtype-Specific Il-6 Family Cytokine-Mediated Vegf Secretion, Ken Tawara, Hannah Scott, Jacqueline Emathinger, Alex Ide, Ryan Fox, Daniel Greiner, Dollie Lajoie, Danielle Hedeen, Madhuri Nandakumar, Andrew J. Oler, Ryan Holzer, Cheryl Jorcyk

Biology Faculty Publications and Presentations

Breast cancer cell-response to inflammatory cytokines such as interleukin-6 (IL-6) and oncostatin M (OSM) may affect the course of clinical disease in a cancer subtype-dependent manner. Furthermore, vascular endothelial growth factor A (VEGF) secretion induced by IL-6 and OSM may also be subtype-dependent. Utilizing datasets from Oncomine, we show that poor survival of invasive ductal carcinoma (IDC) breast cancer patients is correlated with both high VEGF expression and high cytokine or cytokine receptor expression in tumors. Importantly, epidermal growth factor receptor-negative (HER2-), but not HER2-positive (HER2+), patient survival is significantly lower with high tumor co-expression of VEGF and OSM, OSMRβ, …

Gateway Scholarships In Biological Sciences: Year 2 Annual Report, Vicki Stieha, Julia Oxford, Amy Ulappa, Brittnee Earl, Jennifer Forbey, Kevin Feris, Jocelyn Cullers

Biology Faculty Publications and Presentations

This report summarizes grant activities, progress toward goals, and broader impacts of the Gateway Scholars Program in the Boise State Department of Biological Sciences during the 2018-19 academic year.

Preferences Of Specialist And Generalist Mammalian Herbivores For Mixtures Versus Individual Plant Secondary Metabolites, Jordan D. Nobler, Jennifer S. Forbey

Biology Faculty Publications and Presentations

Herbivores that forage on chemically defended plants consume complex mixtures of plant secondary metabolites (PSMs). However, the mechanisms by which herbivores tolerate mixtures of PSMs are relatively poorly understood. As such, it remains difficult to predict how PSMs, singly or as complex mixtures, influence diet selection by herbivores. Although relative rates of detoxification of PSMs have been used to explain tolerance of PSMs by dietary specialist herbivores, few studies have used the rate of detoxification of individual PSMs to understand dietary preferences of individual herbivores for individual versus mixtures of PSMs. We coupled in vivo experiments using captive feeding trials …

A Fragment Of Apolipoprotein E4 Leads To The Downregulation Of A Cxorf56 Homologue, A Novel Er-Associated Protein, And Activation Of Bv2 Microglial Cells, Tanner B. Pollock, Jacob M. Mack, Noail F. Isho, Raquel J. Brown, Alexandra E. Oxford, Brad E. Morrison, Eric J. Hayden, Troy T. Rohn

Biology Faculty Publications and Presentations

Despite the fact that harboring the apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer’s disease (AD), the exact mechanism by which apoE4 contributes to disease progression remains unknown. Recently, we demonstrated that a 151 amino-terminal fragment of apoE4 (nApoE4_1-151) localizes within the nucleus of microglia in the human AD brain, suggesting a potential role in gene expression. In the present study, we investigated this possibility utilizing BV2 microglia cells treated exogenously with nApoE4_1-151. The results indicated that nApoE4_1-151 leads to morphological activation of microglia cells through, at least in part, …

The Role Of Antarctica In Biogeographical Reconstruction: A Point Of View, Manuel De La Estrella, Sven Buerki, Thais Vasconcelos, Eve J. Lucas, Félix Forest

Biology Faculty Publications and Presentations

Premise of research. The opening of the Drake Passage in the Miocene (disconnecting Antarctica and South America and resulting in the establishment of the Circumpolar Current preventing warm waters from the north to reach the polar continent) has led to the formation of the ice sheets and the retreat of the temperate to tropical vegetation that had covered Antarctica for millions of years. With only two current native vascular plant species, Antarctica has been virtually ignored in biogeographical reconstructions and, when considered, only a posteriori invoked as a route of dispersal to reconcile inferred disjunct biogeographical patterns.

Methodology. Here, we …

Despite Similar Perceptions And Attitudes, Postbaccalaureate Students Outperform In Introductory Biology And Chemistry Courses, Erin E. Shortlidge, Liz Rain-Griffith, Chloe Shelby, Gwen Shusterman, Jack Barbera

Biology Faculty Publications and Presentations

Embedding active learning is a common mechanism for meeting science, technology, engineering, and mathematics (STEM) education reform goals. Researchers have identified student benefits from such strategies, yet these benefits may not be universal for all students. We sought to identify how students at a nontraditional university perceive introductory biology and chemistry courses, and whether perceptions relate to course type, performance, or student status. We surveyed students (n = 601) using open-ended prompts regarding their perceptions of factors that impact their learning and interest, and about specific learning strategies. Generally, students did not differ in what influenced their learning or …

Disruption Of Cul3-Mediated Ubiquitination Causes Proximal Tubule Injury And Kidney Fibrosis, Turgay Saritas, Catherina A. Cuevas, Mohammed Z. Ferdaus, Christophe Kuppe, Rafael Kramann, Marcus J. Moeller, Jurgen Floege, Jeffrey Singer, James A. Mccormick

Biology Faculty Publications and Presentations

Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury. The cdk2-cyclin E inhibitor roscovitine did not prevent the effects …

Cullin-3 Dependent Deregulation Of Actn1 Represents A New Pathogenic Mechanism In Nemaline Myopathy, Jordan Blondelle, Kavya Tallapaka, Jane T. Seto, Majid Ghassemian, Madison Clark, Jenni M. Laitila, Adam Bournazos, Jeffrey Singer, Stephan Lange

Biology Faculty Publications and Presentations

Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy, and presence of nemaline bodies within myofibers. However, understanding of the underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40, and KLHL41, three substrate adaptors for the E3 ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. We hypothesized that deregulation of Cullin-3 and its muscle protein substrates may be responsible for disease development. Using Cullin-3–knockout mice, we identified accumulation of non-muscle α-actinins (ACTN1 and ACTN4) in muscles of these mice, which we also observed in patients with mutations in KBTBD13. Our …

Differential Activity Of Coexisting Prochlorococcus Ecotypes, Anne Thompson, Kathleen Kouba

Biology Faculty Publications and Presentations

The abundance and widespread distribution of the unicellular cyanobacterium Prochlorococcus is attributed to its extensive genetic diversity. At least twelve distinct clades, or ecotypes, of Prochlorococcus have been discovered so far, and follow distinct distribution patterns over horizontal and vertical gradients in the oligotrophic ocean. However, multiple ecotypes (and sub-ecotypes) of Prochlorococcus always coexist in varying proportions. While laboratory experiments and genomic analysis suggest that ecotypes contribute differently to biogeochemical cycles, no studies have tested the differential activity of coexisting ecotypes in natural assemblages of Prochlorococcus. Here, we performed DNA stable isotope probing (DNA-SIP) experiments in on-deck incubations of oceanic …

Mitosrnas And Extreme Anoxia Tolerance In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Claire L. Riggs, Steven Cody Woll, Jason Podrabsky

Biology Faculty Publications and Presentations

Embryos of the annual killifish Austrofundulus limnaeus are the most anoxia-tolerant vertebrate. Annual killifish inhabit ephemeral ponds, producing drought and anoxia-tolerant embryos, which allows the species to persist generation after generation. Anoxia tolerance and physiology vary by developmental stage, creating a unique opportunity for comparative study within the species. A recent study of small ncRNA expression in A. limnaeus embryos in response to anoxia and aerobic recovery revealed small ncRNAs with expression patterns that suggest a role in supporting anoxia tolerance. MitosRNAs, small ncRNAs derived from the mitochondrial genome, emerged as an interesting group of these sequences. MitosRNAs derived from …

Review: Using Physiologically Based Models To Predict Population Responses To Phytochemicals By Wild Vertebrate Herbivores, J. S. Forbey, T. T. Caughlin

Biology Faculty Publications and Presentations

To understand how foraging decisions impact individual fitness of herbivores, nutritional ecologists must consider the complex in vivo dynamics of nutrient–nutrient interactions and nutrient–toxin interactions associated with foraging. Mathematical modeling has long been used to make foraging predictions (e.g. optimal foraging theory) but has largely been restricted to a single currency (e.g. energy) or using simple indices of nutrition (e.g. fecal nitrogen) without full consideration of physiologically based interactions among numerous co-ingested phytochemicals. Here, we describe a physiologically based model (PBM) that provides a mechanistic link between foraging decisions and demographic consequences. Including physiological mechanisms of absorption, digestion and metabolism …

Dynamics Of Prochlorococcus Diversity And Photoacclimation During Short-Term Shifts In Water Column Stratification At Station Aloha, Anne W. Thompson, Ger Van Den Engh, Nathan A. Ahlgren, Kathleen Kouba, Samantha Ward, Samuel T. Wilson, David M. Karl

Biology Faculty Publications and Presentations

The cyanobacterium Prochlorococcus is the dominant phototroph in surface waters of the vast oligotrophic oceans, the foundation of marine food webs, and an important component of global biogeochemical cycles. The prominence of Prochlorococcus across the environmental gradients of the open ocean is attributed to its extensive genetic diversity and flexible chlorophyll physiology, enabling light capture over a wide range of intensities. What remains unknown is the balance between temporal dynamics of genetic diversity and chlorophyll physiology in the ability of Prochlorococcus to respond to a variety of short (approximately 1 day) and longer (months to year) changes in the environment. …

Modeling How Land Use Legacy Affects The Provision Of Ecosystem Services In Mediterranean Southern Spain, Juan Miguel Requena-Mullor, Cristina Quintas-Soriano, Jodi Brandt, Javier Cabello, Antonio J. Castro

Biology Faculty Publications and Presentations

Land use decisions induce legacies that affect the welfare of future generations. Here, we present a spatial modeling approach for quantifying how past land use decisions influence provision of multiple ecosystem services(ESs) based on different land use trajectories. We modeled the effect of past land use changes on water regulation, soil protection and habitat quality in southern Spain, one of the most transformed areas of the Mediterranean region. We demonstrate a measurable influence of antecedent land use changes on the capacity of a given land use to provide ESs, and that the effect size can vary among different services and …

Dual Gain And Loss Of Cullin 3 Function Mediates Familial Hyperkalemic Hypertension, Ryan J. Cornelius, Chang Zhang, Kayla J. Erspamer, Larry N. Agbor, Curt D. Sigmund, Jeffrey Singer, Chao-Ling Yang, David H. Ellison

Biology Faculty Publications and Presentations

Familial hyperkalemic hypertension is caused by mutations in with-no-lysine kinases (WNKs) or in proteins that mediate their degradation, kelch-like 3 (KLHL3) and cullin 3 (CUL3). Although the mechanisms by which WNK and KLHL3 mutations cause the disease are now clear, the effects of the disease-causing CUL3Δ403-459 mutation remain controversial. Possible mechanisms, including hyperneddylation, altered ubiquitin ligase activity, decreased association with the COP9 signalosome (CSN), and increased association with and degradation of KLHL3 have all been postulated. Here, we systematically evaluated the effects of Cul3Δ403-459 using cultured kidney cells. We first identified that the catalytically active CSN subunit jun activation domain-binding …