Electrokinetic Mixing for Improving the Kinetics of an HbA1c Immunoassay.
AuthorsYasun E, Trusty T, Abolhosn RW, Clarke NJ, Mezic I
JournalSci Rep
PubMed ID31882622
'The efficiency of the diagnostic platforms utilizing ELISA technique or immunoassays depends highly on incubation times of the recognition elements or signaling molecules and volume of the patient samples. In conventional immunoassays, long incubation times and excess amounts of the recognition and signaling molecules are used. The technology proposed here ... More
TGFß2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells.
AuthorsCorbet C, Bastien E, Santiago de Jesus JP, Dierge E, Martherus R, Vander Linden C, Doix B, Degavre C, Guilbaud C, Petit L, Michiels C, Dessy C, Larondelle Y, Feron O
JournalNat Commun
PubMed ID31974393
'Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-ß2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-ß2 signaling, which in turn favors the formation of ... More
Proliferative regulation of alveolar epithelial type 2 progenitor cells by human
AuthorsZhao R, Ali G, Chang J, Komatsu S, Tsukasaki Y, Nie HG, Chang Y, Zhang M, Liu Y, Jain K, Jung BG, Samten B, Jiang D, Liang J, Ikebe M, Matthay MA, Ji HL
SORLA regulates endosomal trafficking and oncogenic fitness of HER2.
AuthorsPietilä M, Sahgal P, Peuhu E, Jäntti NZ, Paatero I, Närvä E, Al-Akhrass H, Lilja J, Georgiadou M, Andersen OM, Padzik A, Sihto H, Joensuu H, Blomqvist M, Saarinen I, Boström PJ, Taimen P, Ivaska J
JournalNat Commun
PubMed ID31138794
'The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the ... More
Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer's disease.
'ApoE4 genotype is the most prevalent and also clinically most important risk factor for late-onset Alzheimer''s disease (AD). Available evidence suggests that the root cause for this increased risk is a trafficking defect at the level of the early endosome. ApoE4 differs from the most common ApoE3 isoform by a ... More
Development of a sandwich ELISA to detect Leishmania 40S ribosomal protein S12 antigen from blood samples of visceral leishmaniasis patients.
AuthorsZhang WW, Ghosh AK, Mohamath R, Whittle J, Picone A, Lypaczewski P, Ndao M, Howard RF, Das P, Reed SG, Matlashewski G
JournalBMC Infect Dis
PubMed ID30285653
'Visceral leishmaniasis (VL), caused by Leishmania donovani complex parasites, is a neglected parasitic disease that is generally fatal if untreated. Despite decades of research to develop a sensitive VL diagnostic test, definitive diagnosis of VL still mainly relies on the visualization of the parasite in aspirates from the spleen, liver ... More
The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins.
AuthorsKim ST, Lee YJ, Tasaki T, Hwang J, Kang MJ, Yi EC, Kim BY, Kwon YT
JournalPLoS One
PubMed ID30157281
'The N-end rule pathway is a proteolytic system in which single N-terminal amino acids of proteins act as a class of degrons (N-degrons) that determine the half-lives of proteins. We have previously identified a family of mammals N-recognins (termed UBR1, UBR2, UBR4/p600, and UBR5/EDD) whose conserved UBR boxes bind N-degrons ... More
A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective Strategy for Ovarian Cancer.
AuthorsShivange G, Urbanek K, Przanowski P, Perry JSA, Jones J, Haggart R, Kostka C, Patki T, Stelow E, Petrova Y, Llaneza D, Mayo M, Ravichandran KS, Landen CN, Bhatnagar S, Tushir-Singh J
JournalCancer Cell
PubMed ID30107179
Therapeutic antibodies targeting ovarian cancer (OvCa)-enriched receptors have largely been disappointing due to limited tumor-specific antibody-dependent cellular cytotoxicity. Here we report a symbiotic approach that is highly selective and superior compared with investigational clinical antibodies. This bispecific-anchored cytotoxicity activator antibody is rationally designed to instigate "cis" and "trans" cytotoxicity by ... More
The C-terminal helix 9 motif in rat cannabinoid receptor type 1 regulates axonal trafficking and surface expression.
AuthorsFletcher-Jones A, Hildick KL, Evans AJ, Nakamura Y, Wilkinson KA, Henley JM
JournalElife
PubMed ID31036155
Cannabinoid type one receptor (CB1R) is only stably surface expressed in axons, where it downregulates neurotransmitter release. How this tightly regulated axonal surface polarity is established and maintained is unclear. To address this question, we used time-resolved imaging to determine the trafficking of CB1R from biosynthesis to mature polarised localisation ... More
GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABA
AuthorsHui KK, Takashima N, Watanabe A, Chater TE, Matsukawa H, Nekooki-Machida Y, Nilsson P, Endo R, Goda Y, Saido TC, Yoshikawa T, Tanaka M
JournalSci Adv
PubMed ID30989111
Dysfunctional mTOR signaling is associated with the pathogenesis of neurodevelopmental and neuropsychiatric disorders. However, it is unclear what molecular mechanisms and pathogenic mediators are involved and whether mTOR-regulated autophagy continues to be crucial beyond neurodevelopment. Here, we selectively deleted ... More
Cytokine-induced translocation of GRP78 to the plasma membrane triggers a pro-apoptotic feedback loop in pancreatic beta cells.
AuthorsVig S, Buitinga M, Rondas D, Crèvecoeur I, van Zandvoort M, Waelkens E, Eizirik DL, Gysemans C, Baatsen P, Mathieu C, Overbergh L,
JournalCell Death Dis
PubMed ID30952835
The 78-kDa glucose-regulated protein (GRP78) is an ubiquitously expressed endoplasmic reticulum chaperone, with a central role in maintaining protein homeostasis. Recently, an alternative role for GRP78 under stress conditions has been proposed, with stress-induced extracellular secretion and translocation of GRP78 to the cell surface where it acts as a multifunctional ... More
The Na/K-ATPase a1 and c-Src form signaling complex under native condition: A crosslinking approach.
AuthorsNie Y, Bai F, Chaudhry MA, Pratt R, Shapiro JI, Liu J
JournalSci Rep
PubMed ID32265464
The protein-protein interactions amongst the Na/K-ATPase a1 subunit, c-Src, and caveolin-1 (cav-1) are essential for the Na/K-ATPase signaling functions. However, there are arguments concerning the interaction model. The present study aims to clarify the interactions amongst the endogenous native proteins in live cells under native resting condition. Under native condition, ... More
IRE1a kinase-mediated unconventional protein secretion rescues misfolded CFTR and pendrin.
AuthorsPark H, Shin DH, Sim JR, Aum S, Lee MG
JournalSci Adv
PubMed ID32128399
The most prevalent pathogenic mutations in the
CD16 pre-ligation by defucosylated tumor-targeting mAb sensitizes human NK cells to ?
AuthorsCapuano C, Pighi C, Maggio R, Battella S, Morrone S, Palmieri G, Santoni A, Klein C, Galandrini R
JournalCancer Immunol Immunother
PubMed ID31950225
Obinutuzumab is a glycoengineered tumor-targeting anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for the Fc?RIIIA/CD16 receptor, which was recently approved for clinical use in CLL and follicular lymphoma. Here we extend our previous observation that, in human NK cells, the sustained CD16 ligation ... More