• The 14-3-3 proteins in regulation of cellular metabolism 

      Kleppe, Rune; Martinez, Aurora; Døskeland, Stein Ove; Haavik, Jan (Peer reviewed; Journal article, 2011-09)
      Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes involved in amino acid metabolism. In the following decades, 14-3-3s have been shown to be involved in many different signaling pathways that ...
    • Cell Death inducing microbial protein phosphatase inhibitors-mechanisms of action 

      Kleppe, Rune; Herfindal, Lars; Døskeland, Stein Ove (Peer reviewed; Journal article, 2015-10-22)
      Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the ...
    • Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis 

      Gausdal, Gro; Wergeland, Anita; Skavland, Jørn; Nguyen, Eric; Pendino, Frédéric; Rouhee, Nazanin; McCormack, Emmet; Herfindal, Lars; Kleppe, Rune; Havemann, Ursula; Schwede, Frank; Bruserud, Øystein; Gjertsen, Bjørn Tore; Lanotte, Michel; Ségal-Bendirdjian, Evelyne; Døskeland, Stein Ove (Peer reviewed; Journal article, 2013)
      We show that cyclic AMP (cAMP) elevating agents protect blasts from patients with acute promyelocytic leukemia (APL) against death induced by first-line anti-leukemic anthracyclines like daunorubicin (DNR). The cAMP effect ...
    • Epistatic and gene wide effects in YWHA and aromatic amino hydroxylase genes across ADHD and other common neuropsychiatric disorders: Association with YWHAE 

      Jacobsen, Kaya Kvarme; Kleppe, Rune; Johansson, Stefan; Zayats, Tetyana; Haavik, Jan (Peer reviewed; Journal article, 2015-09)
      Monoamines critically modulate neurophysiological functions affected in several neuropsychiatric disorders. We therefore examined genes encoding key enzymes of catecholamine and serotonin biosynthesis (tyrosine and tryptophan ...
    • Exome chip analyses in adult attention deficit hyperactivity disorder 

      Zayats, Tetyana; Jacobsen, Kaya Kvarme; Kleppe, Rune; Jacob, CP; Kittel-Schneider, Sarah; Ribases, Marta; Ramos-Quiroga, JA; Richarte, Vanesa; Casas, M; Mota, NR; Grevet, EH; Klein, M; Corominas, J; Bralten, Janita; Galesloot, T; Vasquez, AA; Herms, S; Forstner, AJ; Larsson, H; Breen, G; Asherson, P; Gross-Lesch, Silke; Lesch, KP; Cichon, Sven; Gabrielsen, Maiken Elvestad; Holmen, Oddgeir Lingaas; Bau, CH; Buitelaar, Jan; Kiemeney, L; Faraone, Stephen V.; Cormand, B; Franke, Barbara; Reif, Andreas; Haavik, Jan; Johansson, Stefan (Peer reviewed; Journal article, 2016)
      Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. ...
    • Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in dopa-responsive dystonia 

      Fossbakk, Agnete; Kleppe, Rune; Knappskog, Per; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2014-06-03)
      Congenital tyrosine hydroxylase deficiency (THD) is found in autosomal-recessive Dopa-responsive dystonia and related neurological syndromes. The clinical manifestations of THD are variable, ranging from early-onset lethal ...
    • GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production 

      Mahootchi, Elaheh; Homaei, Selina Cannon; Kleppe, Rune; Winge, Ingeborg; Hegvik, Tor-Arne; Perez, Roberto Megias; Totland, Christian; Mogavero, Floriana; Baumann, Anne; Glennon, Jeffrey Colm; Miletic, Hrvoje; Kursula, Petri; Haavik, Jan (Journal article; Peer reviewed, 2020)
      Carnosine and related β-alanine–containing peptides are believed to be important antioxidants, pH buffers, and neuromodulators. However, their biosynthetic routes and therapeutic potential are still being debated. This ...
    • In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins 

      Pakdaman, Yasaman; Sanchez Guixe, Monica; Kleppe, Rune; Erdal, Sigrid; Bustad, Helene J.; Bjørkhaug, Lise; Haugarvoll, Kristoffer; Tzoulis, Charalampos; Heimdal, Ketil Riddervold; Knappskog, Per; Johansson, Stefan; Aukrust, Ingvild (Peer reviewed; Journal article, 2017)
      Spinocerebellar ataxia, autosomal recessive 16 (SCAR16) is caused by biallelic mutations in the STIP1 homology and U-box containing protein 1 (STUB1) gene encoding the ubiquitin E3 ligase and dimeric co-chaperone C-terminus ...
    • Increased microvascular permeability in mice lacking Epac1 (Rapgef3) 

      Kopperud, Reidun Kristin; Rygh, Cecilie Brekke; Karlsen, Tine Veronica; Krakstad, Camilla; Kleppe, Rune; Høivik, Erling Andre; Bakke, Marit; Tenstad, Olav; Selheim, Frode; Liden, Åsa; Madsen, Lise; Pavlin, Tina; Taxt, Torfinn; Kristiansen, K.; Curry, FE; Reed, Rolf K.; Doskeland, Stein Ove (Peer reviewed; Journal article, 2017-02)
      Aim: Maintenance of the blood and extracellular volume requires tight control of endothelial macromolecule permeability, which is regulated by cAMP signalling. This study probes the role of the cAMP mediators rap guanine ...
    • Introduction of aromatic ring-containing substituents in cyclic nucleotides is associated with inhibition of toxin uptake by the hepatocyte transporters OATP 1B1 and 1B3 

      Herfindal, Lars; Krakstad, Camilla; Myhren, Lene Elisabeth; Hagland, Hanne; Kopperud, Reidun Kristin; Teigen, Knut; Schwede, Frank; Kleppe, Rune; Døskeland, Stein Ove (Peer reviewed; Journal article, 2014-04-16)
      Analogs of the cyclic nucleotides cAMP and cGMP have been extensively used to mimic or modulate cellular events mediated by protein kinase A (PKA), Exchange protein directly activated by cAMP (Epac), or protein kinase G ...
    • Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression 

      Winge, Ingeborg; Teigen, Knut; Fossbakk, Agnete; Mahootchi, Elaheh; Kleppe, Rune; Sköldberg, Filip; Kämpe, Olle; Haavik, Jan (Peer reviewed; Journal article, 2015-11)
      Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have ...
    • Mathematical modelling of nitric oxide/cyclic GMP/cyclic AMP signalling in platelets 

      Kleppe, Rune; Jonassen, Inge; Doskeland, Stein Ove; Selheim, Frode (Peer reviewed; Journal article, 2018-02-19)
      Platelet activation contributes to normal haemostasis but also to pathologic conditions like stroke and cardiac infarction. Signalling by cGMP and cAMP inhibit platelet activation and are therefore attractive targets for ...
    • Modelling cellular signal communication mediated by phosphorylation dependent interaction with 14-3-3 proteins 

      Kleppe, Rune; Ghorbani, Sadaf; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2014-01-03)
      The 14-3-3 proteins are important effectors of Ser/Thr phosphorylation in eukaryotic cells. Using mathematical modelling we investigated the roles of these proteins as effectors in signalling pathways that involve ...
    • Phosphorylation at serine 31 targets tyrosine hydroxylase tovesicles for transport along microtubules 

      Jorge Finnigan, Ana; Kleppe, Rune; K C, Kunwar Jung; Ying, Ming; Marie, Michael Bruno Eric; Rios Mondragon, Ivan; Salvatore, Michael F; Saraste, Jaakko; Martinez, Aurora (Peer reviewed; Journal article, 2017)
      Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-DOPA, which is the rate-limiting step in the synthesis of catecholamines, such as dopamine, in dopaminergergic neurons. Low dopamine levels and death ...
    • Regulation of tyrosine hydroxylase is preserved across different homo- and heterodimeric 14-3-3 proteins 

      Ghorbani, Sadaf; Fossbakk, Agnete; Jorge Finnigan, Ana; Flydal, Marte Innselset; Haavik, Jan; Kleppe, Rune (Peer reviewed; Journal article, 2016-05)
      Tyrosine hydroxylase (TH) is regulated by members of the 14-3-3 protein family. However, knowledge about the variation between 14-3-3 proteins in their regulation of TH is still limited. We examined the binding, effects ...
    • Serine 19 phosphorylation and 14‐3‐3 binding regulate phosphorylation and dephosphorylation of tyrosine hydroxylase on serine 31 and serine 40 

      Ghorbani, Sadaf; Szigetvari, Peter Daniel; Haavik, Jan; Kleppe, Rune (Peer reviewed; Journal article, 2019-09-17)
      Multisite phosphorylation and structural flexibility allow for complex regulation of proteins through cellular signaling. Tyrosine hydroxylase (TH), a key enzyme of catecholamine synthesis, is regulated by multiple neuronal ...
    • Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease 

      Waløen, Kai; Kleppe, Rune; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2017)
      Introduction: The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine ...
    • Tyrosinemia Type 1 and symptoms of ADHD: Biochemical mechanisms and implications for treatment and prognosis 

      Barone, Helene; Bliksrud, Yngve Thomas; Elgen, Irene Bircow; Szigetvari, Peter Daniel; Kleppe, Rune; Ghorbani, Sadaf; Hansen, Eirik Vangsøy; Haavik, Jan (Peer reviewed; Journal article, 2019-10-21)
      Hereditary tyrosinemia Type 1 (HT‐1) is a rare metabolic disease where the enzyme catalyzing the final step of tyrosine breakdown is defect, leading to accumulation of toxic metabolites. Nitisinone inhibits the degradation ...