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A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol

Melanie Gertz, Giang Thi Tuyet Nguyen, Frank Fischer, Benjamin Suenkel, Christine Schlicker, Benjamin Fränzel, Jana Tomaschewski, Firouzeh Aladini, Christian Becker, Dirk Wolters, Clemens Steegborn, Michael Massiah
2012 PLoS ONE  
Sirtuins are protein deacetylases regulating metabolism, stress responses, and aging processes, and they were suggested to mediate the lifespan extending effect of a low calorie diet. Sirtuin activation by the polyphenol resveratrol can mimic such lifespan extending effects and alleviate metabolic diseases. The mechanism of Sirtuin stimulation is unknown, hindering the development of improved activators. Here we show that resveratrol inhibits human Sirt3 and stimulates Sirt5, in addition to
more » ... 1, against fluorophore-labeled peptide substrates but also against peptides and proteins lacking the non-physiological fluorophore modification. We further present crystal structures of Sirt3 and Sirt5 in complex with fluorogenic substrate peptide and modulator. The compound acts as a top cover, closing the Sirtuin's polypeptide binding pocket and influencing details of peptide binding by directly interacting with this substrate. Our results provide a mechanism for the direct activation of Sirtuins by small molecules and suggest that activators have to be tailored to a specific Sirtuin/substrate pair.
doi:10.1371/journal.pone.0049761 pmid:23185430 pmcid:PMC3504108 fatcat:jrgyi2j4w5bkdpxxihbwgnwd4e

The histone chaperone ASF1 is essential for sexual development in the filamentous fungus Sordaria macrospora

Stefan Gesing, Daniel Schindler, Benjamin Fränzel, Dirk Wolters, Minou Nowrousian
2012 Molecular Microbiology  
Ascomycetes develop four major types of fruiting bodies that share a common ancestor, and a set of common core genes most likely controls this process. One way to identify such genes is to search for conserved expression patterns. We analysed microarray data of Fusarium graminearum and Sordaria macrospora, identifying 78 genes with similar expression patterns during fruiting body development. One of these genes was asf1 (anti-silencing function 1), encoding a predicted histone chaperone. asf1
more » ... pression is also upregulated during development in the distantly related ascomycete Pyronema confluens. To test whether asf1 plays a role in fungal development, we generated an S. macrospora asf1 deletion mutant. The mutant is sterile and can be complemented to fertility by transformation with the wild-type asf1 and its P. confluens homologue. An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast twohybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. Several developmental genes are dependent on asf1 for correct transcriptional expression. Deletion of the histone chaperone genes rtt106 and cac2 did not cause any developmental phenotypes. These data indicate that asf1 of S. macrospora encodes a conserved histone chaperone that is required for fruiting body development.
doi:10.1111/j.1365-2958.2012.08058.x pmid:22463819 fatcat:tcxpedyzrjfgdmbsvymdkm7bf4

Identification of a Chloroplast Ribonucleoprotein Complex ContainingTrans-splicing Factors, Intron RNA, and Novel Components

Jessica Jacobs, Christina Marx, Vera Kock, Olga Reifschneider, Benjamin Fränzel, Christoph Krisp, Dirk Wolters, Ulrich Kück
2013 Molecular & Cellular Proteomics  
Maturation of chloroplast psaA pre-mRNA from the green alga Chlamydomonas reinhardtii requires the trans-splicing of two split group II introns. Several nuclear-encoded trans-splicing factors are required for the correct processing of psaA mRNA. Among these is the recently identified Raa4 protein, which is involved in splicing of the tripartite intron 1 of the psaA precursor mRNA. Part of this tripartite group II intron is the chloroplast encoded tscA RNA, which is specifically bound by Raa4.
more » ... ing Raa4 as bait in a combined tandem affinity purification and mass spectrometry approach, we identified core components of a multisubunit ribonucleoprotein complex, including three previously identified trans-splicing factors (Raa1, Raa3, and Rat2). We further detected tscA RNA in the purified protein complex, which seems to be specific for splicing of the tripartite group II intron. A yeast-two hybrid screen and co-immunoprecipitation identified chloroplast-localized Raa4-binding protein 1 (Rab1), which specifically binds tscA RNA from the tripartite psaA group II intron. The yeast-two hybrid system provides evidence in support of direct interactions between Rab1 and four trans-splicing factors. Our findings contribute to our knowledge of chloroplast multisubunit ribonucleoprotein complexes and are discussed in support of the generally accepted view that group II introns are the ancestors of the eukaryotic spliceosomal introns. Molecular & Cellular Proteomics 1 The abbreviations used are: CRM, chloroplast RNA-splicing and ribosome maturation; EMSA, electrophoretic mobility shift assay; MudPIT, multidimensional protein identification technology; Ni-NTA, nickel-nitrilotriacetic acid; qRT-PCR, quantitative real-time PCR; SD, synthetic dropout; snRNA, small nuclear RNA; TAP, tandem affinity purification. Research
doi:10.1074/mcp.m112.026583 pmid:23559604 pmcid:PMC3708175 fatcat:n55p6e774nb2njzhbdp2oc3bku

Biochemical Large-Scale Interaction Analysis of Murine Olfactory Receptors and Associated Signaling Proteins with Post-Synaptic Density 95, Drosophila Discs Large, Zona-Occludens 1 (PDZ) Domains

Fabian Jansen, Benjamin Kalbe, Paul Scholz, Benjamin Fränzel, Markus Osterloh, Dirk Wolters, Hanns Hatt, Eva Maria Neuhaus, Sabrina Osterloh
2015 Molecular & Cellular Proteomics  
G protein-coupled receptors (GPCRs) constitute the largest family among mammalian membrane proteins and are capable of initiating numerous essential signaling cascades. Various GPCR-mediated pathways are organized into protein microdomains that can be orchestrated and regulated through scaffolding proteins, such as PSD-95/ discs-large/ZO1 (PDZ) domain proteins. However, detailed binding characteristics of PDZ-GPCR interactions remain elusive because these interactions seem to be more complex
more » ... n previously thought. To address this issue, we analyzed binding modalities using our established model system. This system includes the 13 individual PDZ domains of the multiple PDZ domain protein 1 (MUPP1; the largest PDZ protein), a broad range of murine olfactory receptors (a multifaceted gene cluster within the family of GPCRs), and associated olfactory signaling proteins. These proteins were analyzed in a large-scale peptide microarray approach and continuative interaction studies. As a result, we demonstrate that canonical binding motifs were not overrepresented among the interaction partners of MUPP1. Furthermore, C-terminal phosphorylation and distinct amino acid replacements abolished PDZ binding promiscuity. In addition to the described in vitro experiments, we identified new interaction partners within the murine olfactory epithelium using pulldown-based interactomics and could verify the partners through co-immunoprecipitation. In summary, the present study provides important insight into the complexity of the
doi:10.1074/mcp.m114.045997 pmid:25979994 pmcid:PMC4528238 fatcat:3h6p5fsfzzavxbh733d5vvho3m

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

Steffen Nordzieke, Thomas Zobel, Benjamin Fränzel, Dirk A. Wolters, Ulrich Kück, Ines Teichert
2014 Eukaryotic Cell  
S arco l emmal m embrane- a ssociated p rotein (SLMAP) is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. Further, SLMAP misexpression is associated with endothelial dysfunctions in diabetes and cancer. SLMAP is part of the conserved str iatin- i nteracting p hosphatase a nd k inase (STRIPAK) complex required for specific signaling pathways in yeasts, filamentous fungi, insects, and mammals. In
more » ... mentous fungi, STRIPAK was initially discovered in Sordaria macrospora , a model system for fungal differentiation. Here, we functionally characterize the STRIPAK subunit PRO45, a homolog of human SLMAP. We show that PRO45 is required for sexual propagation and cell-to-cell fusion and that its f ork h ead- a ssociated (FHA) domain is essential for these processes. Protein-protein interaction studies revealed that PRO45 binds to STRIPAK subunits PRO11 and SmMOB3, which are also required for sexual propagation. Superresolution s tructured- i llumination m icroscopy (SIM) further established that PRO45 localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. SIM also showed that localization to the nuclear envelope requires STRIPAK subunits PRO11 and PRO22, whereas for mitochondria it does not. Taken together, our study provides important insights into fundamental roles of the fungal SLMAP homolog PRO45 and suggests STRIPAK-related and STRIPAK-unrelated functions.
doi:10.1128/ec.00241-14 pmid:25527523 pmcid:PMC4385808 fatcat:np5jp4wdyvcelogunt67ftg6bm

PRO40 Is a Scaffold Protein of the Cell Wall Integrity Pathway, Linking the MAP Kinase Module to the Upstream Activator Protein Kinase C

Ines Teichert, Eva Katharina Steffens, Nicole Schnaß, Benjamin Fränzel, Christoph Krisp, Dirk A. Wolters, Ulrich Kück, Joseph Heitman
2014 PLoS Genetics  
Mitogen-activated protein kinase (MAPK) pathways are crucial signaling instruments in eukaryotes. Most ascomycetes possess three MAPK modules that are involved in key developmental processes like sexual propagation or pathogenesis. However, the regulation of these modules by adapters or scaffolds is largely unknown. Here, we studied the function of the cell wall integrity (CWI) MAPK module in the model fungus Sordaria macrospora. Using a forward genetic approach, we found that sterile mutant
more » ... 30 has a mutated mik1 gene that encodes the MAPK kinase kinase (MAPKKK) of the proposed CWI pathway. We generated single deletion mutants lacking MAPKKK MIK1, MAPK kinase (MAPKK) MEK1, or MAPK MAK1 and found them all to be sterile, cell fusion-deficient and highly impaired in vegetative growth and cell wall stress response. By searching for MEK1 interaction partners via tandem affinity purification and mass spectrometry, we identified previously characterized developmental protein PRO40 as a MEK1 interaction partner. Although fungal PRO40 homologs have been implicated in diverse developmental processes, their molecular function is currently unknown. Extensive affinity purification, mass spectrometry, and yeast two-hybrid experiments showed that PRO40 is able to bind MIK1, MEK1, and the upstream activator protein kinase C (PKC1). We further found that the PRO40 N-terminal disordered region and the central region encompassing a WW interaction domain are sufficient to govern interaction with MEK1. Most importantly, time-and stressdependent phosphorylation studies showed that PRO40 is required for MAK1 activity. The sum of our results implies that PRO40 is a scaffold protein for the CWI pathway, linking the MAPK module to the upstream activator PKC1. Our data provide important insights into the mechanistic role of a protein that has been implicated in sexual and asexual development, cell fusion, symbiosis, and pathogenicity in different fungal systems.
doi:10.1371/journal.pgen.1004582 pmid:25188365 pmcid:PMC4154660 fatcat:g4kt4ususfaslolbkfregys5pa

Qupe—a Rich Internet Application to take a step forward in the analysis of mass spectrometry-based quantitative proteomics experiments

Stefan P. Albaum, Heiko Neuweger, Benjamin Fränzel, Sita Lange, Dominik Mertens, Christian Trötschel, Dirk Wolters, Jörn Kalinowski, Tim W. Nattkemper, Alexander Goesmann
2009 Computer applications in the biosciences : CABIOS  
Fränzel et al., submitted for publication) . The resulting 38 datasets were converted into the open source format mzXML with the tool 'ReAdW' (Keller et al., 2002; Nesvizhskii et al., 2003) .  ... 
doi:10.1093/bioinformatics/btp568 pmid:19808875 fatcat:xjvqxrxl4feglbgadliabizzki

Jugend im Feuer. August 1914 im Serakreis

Meike G. Werner
2014 Zeitschrift für Ideengeschichte  
Walter Fränzel, Brooklyn, 5.  ...  Abgetippt von Walter Fränzel, Glüsingen Weihnachten 1950, S. 65 (Privatarchiv Fränzel, Glüsingen). 9 Martha Hörmanns Brief- sammlung 1935/36. Typo- skript. Bremen o.D.  ... 
doi:10.17104/1863-8937-2014-2-19 fatcat:nrockwr4oreh3gtq6xpb5szwja

Page 296 of National Union Catalog Vol. 27, Issue [page]

1953 National Union Catalog  
Franzel, Augustus, see Strachey, John Francis, 1894- parade. Mayfair Franzell, Carlotta see Bizet, Georges, 1838-1875.  ...  Franklin, Benjamin, 1706-1790, su; composer. Quartet, 3 violins & violoncello, F Quatuor pour trois violons et violoncelle.  ... 

Acknowledgments [chapter]

2022 The Redemption of Things  
Jahrhundert, edited by Michael Bies, Sean Franzel, and Dirk Oschmann (Hannover: Wehrhahn Verlag, 2017).  ...  Abel, Benjamin Schreyer, and Jens Guettel provided support in the final stages of the proj ect, even if that support was more moral (and of course bibulous) than always scholarly.  ... 
doi:10.1515/9781501761584-001 fatcat:d6yhxhjcjvdibhpchwbdx2u7au

Page 163 of Journal of Engineering Education Vol. 47, Issue 6 [page]

1957 Journal of Engineering Education  
Ventura Franzel, E. J. Whittier Thorpe, C. J., 1489 El Terraza COLORADO Aurora USAF Academy Barko, J. S., PéHead,GraphicsDept. Baxter, W. L., Assoc.P.Graphics Clementson, G. C., P.€Hd.Aero.  ...  Benjamin, J. R., Assoc.P.Struc.£. Birnie, H. F., Assoc.P.M.L. Brown, L. H., P.Z.E. Duran, S. A., Act.Assoc.P. Met. Eustis, R. H., Assoc.P.M.E. Edson, W. 6 Cons.P.E.E. Franzini, J. B., Assoc.P.C.E.  ... 

Agroforestry and non-state actors: A review

Joseph Bettles, David S. Battisti, Susan C. Cook-Patton, Timm Kroeger, June T. Spector, Nicholas H. Wolff, Yuta J. Masuda
2021 Forest Policy and Economics  
., 2012; Russell and Franzel, 2004) .  ...  systems through mobile phones (Ogutu et al., 2014; Russell and Franzel, 2004)  ... 
doi:10.1016/j.forpol.2021.102538 fatcat:vy7os2zutngklotfrvzjnveoym

Page 174 of Journal of Engineering Education Vol. 46, Issue 6 [page]

1956 Journal of Engineering Education  
Benjamin, J. R., Assoc.P.Struc.E. Banks, C. W., 1906 138th St. Crawford, I. C., Dir., Colo. Water Consery Bd. Weers, W. A., 3320 Martin Dr. Birnie, H. F., Assoc.P.M.L. U. 8 Brown, L.  ...  Ventura Franzel, BE. J. Ventura Junior College Jones, R. W., Head,Eng. Santa Rosa Williams, P. E., Pers. Cons. Junior College Haentjens, C. H., —_ Math. Ravenscroft, H. Inst.Phys.&éE. Wilcox, J.  ... 

A search asymmetry for interocular conflict

Chris L. E. Paffen, Ignace T. C. Hooge, Jeroen S. Benjamins, Hinze Hogendoorn
2011 Attention, Perception & Psychophysics  
We reconcile our findings with those of Wolfe and Franzel (1988) , who reported inefficient search for interocular conflict (26 ms/item) and found no evidence for a search asymmetry.  ...  What could be the reason that the results of Wolfe and Franzel differ from the ones reported here?  ...  Wolfe and Franzel presented images dichoptically using a rotating shutter that produced 30-Hz flicker.  ... 
doi:10.3758/s13414-011-0100-3 pmid:21336519 pmcid:PMC3089734 fatcat:y2uitlngb5a6blc63j7cn5l7i4

Page 188 of Journal of Engineering Education Vol. 50, Issue 6 [page]

1960 Journal of Engineering Education  
Benjamin, J. R., Assoc.P.Struc.H. Brown, L. H., P.#.E. Cantin, G., PostGrad. StudentEngr.Mech. Eustis, R. H., Assoc.P.M.E. Fondahl, J. W., Asst.P.C.E. Franzini, J.  ...  Navy Air Missile Test Center Franzel, E. J. Dewing, M. M., Dir.Empl.Devel. Vernon Hunterman, H. J., SeniorEngr., Bechtel Corp. Walnut Creek Marmion, K. R., 120 Sequoia Ave. COLORADO Boulder Banks, C.  ... 
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