Functional Studies on the MRP1 Multidrug Transporter: Characterization of ABC-Signature Mutant Variants
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ATP-Binding and Hydrolysis in Inflammasome Activation
molecules Review ATP-Binding and Hydrolysis in Inflammasome Activation Christina F. Sandall, Bjoern K. Ziehr and Justin A. MacDonald * Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; [email protected] (C.F.S.); [email protected] (B.K.Z.) * Correspondence: [email protected]; Tel.: +1-403-210-8433 Academic Editor: Massimo Bertinaria Received: 15 September 2020; Accepted: 3 October 2020; Published: 7 October 2020 Abstract: The prototypical model for NOD-like receptor (NLR) inflammasome assembly includes nucleotide-dependent activation of the NLR downstream of pathogen- or danger-associated molecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomeric platforms that lie upstream of inflammatory responses associated with innate immunity. As members of the STAND ATPases, the NLRs are generally thought to share a similar model of ATP-dependent activation and effect. However, recent observations have challenged this paradigm to reveal novel and complex biochemical processes to discern NLRs from other STAND proteins. In this review, we highlight past findings that identify the regulatory importance of conserved ATP-binding and hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explore recent breakthroughs that generate connections between NLR protein structure and function. Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectives on the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations of NLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctions in nucleotide-binding domain topology with occupancy of ATP or ADP that are in turn disseminated on to the global protein structure. -
ABCB6 Is a Porphyrin Transporter with a Novel Trafficking Signal That Is Conserved in Other ABC Transporters Yu Fukuda University of Tennessee Health Science Center
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 12-2008 ABCB6 Is a Porphyrin Transporter with a Novel Trafficking Signal That Is Conserved in Other ABC Transporters Yu Fukuda University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Chemicals and Drugs Commons, and the Medical Sciences Commons Recommended Citation Fukuda, Yu , "ABCB6 Is a Porphyrin Transporter with a Novel Trafficking Signal That Is Conserved in Other ABC Transporters" (2008). Theses and Dissertations (ETD). Paper 345. http://dx.doi.org/10.21007/etd.cghs.2008.0100. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. ABCB6 Is a Porphyrin Transporter with a Novel Trafficking Signal That Is Conserved in Other ABC Transporters Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Interdisciplinary Program Research Advisor John D. Schuetz, Ph.D. Committee Linda Hendershot, Ph.D. James I. Morgan, Ph.D. Anjaparavanda P. Naren, Ph.D. Jie Zheng, Ph.D. DOI 10.21007/etd.cghs.2008.0100 This dissertation is available at UTHSC Digital Commons: https://dc.uthsc.edu/dissertations/345 ABCB6 IS A PORPHYRIN TRANSPORTER WITH A NOVEL TRAFFICKING SIGNAL THAT -
What's New on Star on Disney+ Parental Controls
March NEWSLETTER Disney+ is the dedicated streaming home for TV series and movies from Disney, Pixar, Marvel, Star Wars, National Geographic and new general entertainment brand Star, including exclusive Disney+ and Star Originals. This newsletter provides regular updates on upcoming Disney+ and Star Originals, brand-new episodes, and the latest blockbuster movies joining the service in the UK. Please note, movie & series availability can vary by country and is subject to change. The below is correct at time of issuing. For general media inquiries, please contact Disney+ UK Press Office Did you know... Robust parental controls will be introduced from 23rd February to ensure that Disney+ remains a suitable viewing experience for everyone in the family. Celebrating one year of Disney+ in Europe - the 24th of March marks one year since we launched in the UK and Ireland! The fifth anniversary of Zootropolis: Revisit this Oscar-winning animation on Disney+ as it turns five this year! Parental Controls: protection + peace of mind Disney+ will remain suitable for audiences of all ages, thanks to the new robust parental controls. From the 23rd February, the app will include easy-to-use parental controls enabling the family-friendly experience to continue. You will be able to set content ratings for individual profiles to restrict access for your younger viewers at home, and set a Profile PIN to keep the kids protected and give parents peace of mind. What’s new on Star on Disney+ Star is the sixth brand to launch on Disney+, joining entertainment favourites Disney, Pixar, Marvel, Star Wars and National Geographic from 23rd February 2021. -
Inhibiting ABCG2 with Sorafenib
Published OnlineFirst May 16, 2012; DOI: 10.1158/1535-7163.MCT-12-0215 Molecular Cancer Therapeutic Discovery Therapeutics New Use for an Old Drug: Inhibiting ABCG2 with Sorafenib Yinxiang Wei1,3, Yuanfang Ma3, Qing Zhao1,4, Zhiguang Ren1,3, Yan Li1, Tingjun Hou2, and Hui Peng1 Abstract Human ABCG2, a member of the ATP-binding cassette transporter superfamily, represents a promising target for sensitizing MDR in cancer chemotherapy. Although lots of ABCG2 inhibitors were identified, none of them has been tested clinically, maybe because of several problems such as toxicity or safety and pharma- cokinetic uncertainty of compounds with novel chemical structures. One efficient solution is to rediscover new uses for existing drugs with known pharmacokinetics and safety profiles. Here, we found the new use for sorafenib, which has a dual-mode action by inducing ABCG2 degradation in lysosome in addition to inhibiting its function. Previously, we reported some novel dual-acting ABCG2 inhibitors that showed closer similarity to degradation-induced mechanism of action. On the basis of these ABCG2 inhibitors with diverse chemical structures, we developed a pharmacophore model for identifying the critical pharmacophore features necessary for dual-acting ABCG2 inhibitors. Sorafenib forms impressive alignment with the pharmacophore hypothesis, supporting the argument that sorafenib is a potential ABCG2 inhibitor. This is the first article that sorafenib may be a good candidate for chemosensitizing agent targeting ABCG2-mediated MDR. This study may facilitate the rediscovery of new functions of structurally diverse old drugs and provide a more effective and safe way of sensitizing MDR in cancer chemotherapy. Mol Cancer Ther; 11(8); 1693–702. -
In Silico Analysis of the TANC Protein Family Received: 3 November 2015 Alessandra Gasparini1,2, Silvio C
www.nature.com/scientificreports OPEN Dynamic scafolds for neuronal signaling: in silico analysis of the TANC protein family Received: 3 November 2015 Alessandra Gasparini1,2, Silvio C. E. Tosatto 2,3, Alessandra Murgia1,4 & Emanuela Leonardi1 Accepted: 2 June 2017 The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify Published online: 28 July 2017 shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scafolds infuencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption. The known Ankyrin and tetratricopeptide repeat (TPR) domains have been modeled. The newly predicted N-terminal ATPase domain may function as a regulated molecular switch for downstream signaling. Several putative conserved protein binding motifs allowed to extend the TANC interaction network. Interestingly, we highlighted connections with diferent signaling pathways converging to modulate neuronal activity. Beyond a known role for TANC family members in the glutamate receptor pathway, they seem linked to planar cell polarity signaling, Hippo pathway, and cilium assembly. This suggests an important role in neuron projection, extension and diferentiation. Neurodevelopmental disorders (NDDs) are common conditions including clinically and genetically heteroge- neous diseases, such as intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy1. Advances in next generation sequencing have identifed a large number of newly arising disease mutations which disrupt convergent molecular pathways involved in neuronal plasticity and synaptic strength2–6. -
Peter Rice Chairman, Walt Disney Television, and Co-Chair, Disney Media Networks the Walt Disney Company Peter Rice Is Chairman
Peter Rice Chairman, Walt Disney Television, and Co-Chair, Disney Media Networks The Walt Disney Company Peter Rice is chairman of Walt Disney Television and co-chair of Disney Media Networks. He oversees The Walt Disney Company’s entertainment and news television properties. This includes ABC, Disney Channels, Freeform, FX and National Geographic networks; ABC Signature, 20th Television and Touchstone Television; and the ABC Owned Television Stations. Rice also oversees The Walt Disney Company’s equity interest in A+E Networks. He reports to Bob Chapek, chairman and CEO, The Walt Disney Company. Prior to his current role, Rice served as president of 21st Century Fox, and chairman and CEO of Fox Networks Group (FNG), where he was instrumental in driving the growth of FNG’s television business across linear and digital platforms. During his tenure, FNG’s revenue doubled as its portfolio was reorganized and aligned around four key brands reaching more than 2 billion subscribers worldwide. At FNG, Rice oversaw long-term sports rights deals with the NFL, MLB, the UFC, FIFA, WWE and dozens of professional sports leagues and teams. He was a driving force in the formation of National Geographic Partners and the launch of FS1 and FS2. He was responsible for realigning its international channels business in Europe, Asia and Latin America, and integrating the company’s advertising divisions into a single, data-driven enterprise. He oversaw the launch of its Digital Consumer Group; its participation in Hulu, where he serves on the board; and the establishment of FoxNext Games. Under Rice’s leadership, FNG was home to shows including “The Simpsons,” “American Idol,” “Glee,” “The Americans,” “Genius,” “Modern Family,” “Homeland,” “This Is Us” and “Empire,” the World Series, the World Cup and the Super Bowl. -
Kaic Cii Ring Flexibility Governs the Rhythm of The
KAIC CII RING FLEXIBILITY GOVERNS THE RHYTHM OF THE CIRCADIAN CLOCK OF CYANOBACTERIA A Dissertation by NAI-WEI KUO Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2011 Major Subject: Biochemistry KAIC CII RING FLEXIBILITY GOVERNS THE RHYTHM OF THE CIRCADIAN CLOCK OF CYANOBACTERIA A Dissertation by NAI-WEI KUO Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved by: Co-Chairs of Committee, Andy LiWang Pingwei Li Committee Members, Deborah Bell-Pedersen Frank Raushel Head of Department, Gregory Reinhart May 2011 Major Subject: Biochemistry iii ABSTRACT KaiC CII Ring Flexibility Governs the Rhythm of the Circadian Clock of Cyanobacteria. (May 2011) Nai-Wei Kuo, B.S.; M.S., National Tsing Hua University, Taiwan Co-Chairs of Advisory Committee: Dr. Andy LiWang, Dr. Pingwei Li The circadian clock orchestrates metabolism and cell division and imposes important consequences to health and diseases, such as obesity, diabetes, and cancer. It is well established that phosphorylation-dependent circadian rhythms are the result of circadian clock protein interactions, which regulate many intercellular processes according to time of day. The phosphorylation-dependent circadian rhythm undergoes a succession of phases: Phosphorylation Phase → Transition Phase → Dephosphorylation Phase. Each phase induces the next phase. However, the mechanism of each phase and how the phosphorylation and dephosphorylation phases are prevented from interfering with each other remain elusive. In this research, we used a newly developed isotopic labeling strategy in combination with a new type of nuclear magnetic resornance (NMR) experiment to obtain the structural and dynamic information of the cyanobacterial KaiABC oscillator system. -
The Walt Disney Company Uk & Ireland
THE WALT DISNEY COMPANY UK & IRELAND Disney has operated in the UK and Ireland for more than 80 years There are nine Disney office locations across the UK and one in Ireland The UK has approximately 30m Disney fans (kids who really like one of our brands and teens/adults who report they strongly or very strongly relate to one of our brands - Disney, Marvel, Star Wars, Nat Geo or Pixar). Source: BES/Kids Tracker/CSR Across the five major European countries (UK, France, Germany, Italy, Spain), there are more than 180m Disney fans. Source: BES/Kids Tracker/CSR Studios In 2019, Disney’s UK box office (£473M, 35% Market Share) was the highest grossing year for a Motion Picture Association studio ever, exceeding 2018. Disney UK had seven of the top ten releases from the year: o #1 Avengers: Endgame (£88.7m) o #2 The Lion King (£76.0m) o #3 Toy Story 4 (£66.2m) o #5 Frozen 2 (£48.5m) o #6 Star Wars: The Rise of Skywalker (£46.9m) o #7 Captain Marvel (£39.5m) o #8 Aladdin (£37.2m) Seven of the top ten biggest films of all time at the UK box office are from Walt Disney Studios titles: o #1 Star Wars: The Force Awakens (£123.2m) o #4 Avatar (£94.0m) o #5 Avengers: Endgame (£88.7m) o #6 Star Wars: The Last Jedi (£82.6m) o #7 Titanic (£80.2m) o #8 The Lion King (£76.0m) o #9 Toy Story 3 (£74.0m) Disney+ Disney+ launched in the UK on March 24th, 2020, on the same day as Ireland, Germany, Spain, Italy, Austria and Switzerland. -
Television Academy Awards
2020 Primetime Emmy® Awards Nomination Press Release Outstanding Character Voice-Over Performance Big Mouth • How To Have An Orgasm • Netflix • Netflix Maya Rudolph as Connie the Hormone Monstress Central Park • Episode One • Apple TV+ • 20th Century Fox Television Leslie Odom, Jr. as Owen Crank Yankers • Bobby Brown, Wanda Sykes & Kathy Griffin • Comedy Central • Kimmelot, ITV, Central Productions, LLC Wanda Sykes as Gladys The Mandalorian • Chapter 8: Redemption • Disney+ • Lucasfilm Ltd. Taika Waititi as IG-11 The Simpsons • Better Off Ned • FOX • Gracie Films in association with 20th Century Fox Television Nancy Cartwright as Bart Simpson, Nelson, Ralph, Todd The Simpsons • Frinkcoin • FOX • Gracie Films in association with 20th Century Fox Television Hank Azaria as Professor Frink, Moe, Chief Wiggum, Carl, Cletus, Kirk, Sea Captain Outstanding Animated Program Big Mouth • Disclosure The Movie: The Musical! • Netflix • Netflix Nick Kroll, Executive Producer Andrew Goldberg, Executive Producer Mark Levin, Executive Producer Jennifer Flackett, Executive Producer Joe Wengert, Co-Executive Producer Kelly Galuska, Supervising Producer Gil Ozeri, Supervising Producer Ben Kalina, Supervising Producer Shannon Prynoski, Supervising Producer Chris Prynoski, Supervising Producer Anthony Lioi, Supervising Producer Mike L. Mayfield, Co-Supervising Director Nate Funaro, Produced by Emily Altman, Producer / Writer Victor Quinaz, Writer Bob Suarez, Director David Bastian, Animation Timer Edgar Larrazabal, Animation Timer Maureen Mlynarczyk, Animation -
BRYCE FORTNER Director of Photography Brycefortner.Com
BRYCE FORTNER Director of Photography brycefortner.com PROJECTS Partial List DIRECTORS STUDIOS/PRODUCERS A MILLION LITTLE THINGS James Griffiths KAPITAL ENTERTAINMENT / ABC Pilot & Season 4 Various Directors Chris Smirnoff, DJ Nash Aaron Kaplan STARGIRL 2 Julia Hart GOTHAM GROUP / DISNEY+ Feature Film Nathan Kelly, Jordan Horowitz Ellen Goldsmith-Vein HELLO, GOODBYE AND EVERYTHING Michael Lewen ACE ENTERTAINMENT IN BETWEEN Feature Film Chris Foss, Max Siemers I’M YOUR WOMAN Julia Hart AMAZON Feature Film Jordan Horowitz, Rachel Brosnahan STARGIRL Julia Hart GOTHAM GROUP / PRINCIPAL DISNEY Feature Film Jim Powers, Jordan Horowitz DOLLFACE Matt Spicer ABC SIGNATURE / HULU Pilot Melanie Elin, Stephanie Laing BROKEN DIAMONDS Peter Sattler BLACK LABEL Feature Film Ellen Schwartz, Mary Sparacio THE MAYOR James Griffiths ABC Pilot Scott Printz, Jean Hester PROFESSOR MARSTON & THE Angela Robinson SONY WONDER WOMEN Terry Leonard, Amy Redford Feature Film Andrea Sperling, Jill Soloway THE TICK Wally Pfister SONY / AMAZON Pilot Kerry Orent, Barry Josephson INGRID GOES WEST Feature Film Matt Spicer STAR THROWER ENTERTAINMENT Official Selection, Sundance Film Festival Jared Goldman HOUSE OF CARDS Wally Pfister NETFLIX Season 4 Promos CHARITY CASE James Griffiths ABC / FOX Pilot Scott Printz, Thea Mann PUNCHING HENRY Feature Film Gregori Viens Ian Coyne, David Permut Official Selection, SXSW Film Festival FLAKED Wally Pfister NETFLIX Series Josh Gordon Tiffany Moore, Mitch Hurwitz Will Arnett TOO LEGIT Short Frankie Shaw Liz Destro Official Selection, -
2018 DGA Episodic Director Diversity Report (By SIGNATORY COMPANY)
2018 DGA Episodic Director Diversity Report (by SIGNATORY COMPANY) Combined # Episodes # Episodes # Episodes # Episodes Combined Total # of Female + Directed by Male Directed by Male Directed by Female Directed by Female Male Male Female Female Signatory Company Title Female + Network Episodes Minority Male Caucasian % Male Minority % Female Caucasian % Female Minority % Unknown Unknown % Unknown Unknown % Minority % Episodes Caucasian Minority Caucasian Minority 40 North Productions, LLC Looming Tower, The 10 0 0% 10 100% 0 0% 0 0% 0 0% 0 0% 0 0% Hulu ABC Signature Studios, Inc. SMILF 8 8 100% 0 0% 0 0% 8 100% 0 0% 0 0% 0 0% Showtime ABC Studios American Housewife 24 13 54% 9 38% 2 8% 11 46% 0 0% 2 8% 0 0% ABC ABC Studios BlacK-ish 24 18 75% 6 25% 11 46% 3 13% 4 17% 0 0% 0 0% ABC ABC Studios Code BlacK 13 6 46% 7 54% 3 23% 2 15% 1 8% 0 0% 0 0% CBS ABC Studios Criminal Minds 22 10 45% 12 55% 4 18% 4 18% 2 9% 0 0% 0 0% CBS ABC Studios For The People 9 4 44% 5 56% 0 0% 2 22% 2 22% 0 0% 0 0% ABC ABC Studios Grey's Anatomy 24 16 67% 8 33% 4 17% 3 13% 9 38% 0 0% 0 0% ABC ABC Studios Grown-ish 13 11 85% 2 15% 7 54% 2 15% 2 15% 0 0% 0 0% Freeform ABC Studios How To Get Away With 15 11 73% 4 27% 2 13% 2 13% 7 47% 0 0% 0 0% ABC Murder ABC Studios Kevin (Probably) Saves the 15 6 40% 9 60% 2 13% 4 27% 0 0% 0 0% 0 0% ABC World ABC Studios Marvel's Agents of 22 11 50% 11 50% 5 23% 4 18% 2 9% 0 0% 0 0% ABC S.H.I.E.L.D. -
Sequence Analysis of the AAA Protein Family
Prorein Science (1997), 62043-2058. Cambridge University Press. Printed in the USA. Copyright 0 1997 The Protein Society REVIEW Sequence analysis of the AAA protein family ANDREAS BEYER Institut fur Physiologische Chemie, Medizinische Fakultat, Ruhr-Universitat. D-44780 Bochum, Germany (RECEIVEDMarch 12, 1997; ACCEPTEDJune 27, 1997) Abstract The AAA protein family, a recently recognized group of Walker-type ATPases, has been subjected to an extensive sequence analysis. Multiple sequence alignments revealed the existence of a region of sequence similarity, the so-called AAA cassette. The borders of this cassette were localized and within it, three boxes of a high degree of conservation were identified. Two of these boxes could be assigned to substantial parts of the ATP binding site (namely, to Walker motifs A and B); the third may be a portion of the catalytic center. Phylogenetic trees were calculated to obtain insights into the evolutionary history of the family. Subfamilies with varying degrees of intra-relatedness could be discriminated; these relationships are also supported by analysis of sequences outside thecanonical AAA boxes: within the cassette are regions that are strongly conserved within each subfamily, whereas little or evenno similarity between different subfamilies can be observed. These regions are well suited to define fingerprints for subfamilies. A secondary structure prediction utilizing all available sequence information was performed and the result was fitted to the general 3D structure of a Walker A/GTPase. The agreement was unexpectedly high and strongly supports the conclusion that the AAA family belongs to the Walker superfamily of A/GTPases. Keywords: AAA family; ATPase; evolution; secondary structure prediction; Walker family The AAA protein family (“triple-A family”) is a group of ATPases SF 6, respectively (see Table 1).