• ATG8 Family Proteins Act as Scaffolds for Assembly of the ULK Complex SEQUENCE REQUIREMENTS FOR LC3-INTERACTING REGION (LIR) MOTIFS 

      Alemu, Endalkachew Ashenafi; Lamark, Trond; Torgersen, Knut Martin; Birgisdottir, Åsa birna; Larsen, Kenneth Bowitz; Jain, Ashish; Olsvik, Hallvard Lauritz; Øvervatn, Aud Karin; Kirkin, Vladimir; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-10-05)
      Autophagy is a lysosome-dependent degradation system conserved among eukaryotes. The mammalian Atg1 homologues, Unc-51 like kinase (ULK) 1 and 2, are multifunctional proteins with roles in autophagy, neurite outgrowth, and vesicle transport. The mammalian ULK complex involved in autophagy consists of ULK1, ULK2, ATG13, FIP200, and ATG101. We have used pulldown and peptide array overlay assays to ...
    • Degradation of arouser by endosomal microautophagy is essential for adaptation to starvation in Drosophila 

      Jacomin, Anne-Claire; Gohel, Raksha; Hussain, Zunoon; Varga, Agnes; Maruzs, Tamas; Eddison, Mark; Sica, Margaux; Jain, Ashish; Moffat, Kevin G.; Johansen, Terje; Jenny, Andreas; Juhasz, Gabor; Nezis, Ioannis (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-12-14)
      Hunger drives food-seeking behaviour and controls adaptation of organisms to nutrient availability and energy stores. Lipids constitute an essential source of energy in the cell that can be mobilised during fasting by autophagy. Selective degradation of proteins by autophagy is made possible essentially by the presence of LIR and KFERQ-like motifs. Using in silico screening of Drosophila ...
    • Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer 

      Puvirajesinghe, Tania M.; Bertucci, François; Jain, Ashish; Scerbo, Pierluigi; Belotti, Edwige; Audebert, Stéphane; Sebbagh, Michael; Lopez, Marc; Brech, Andreas; Finetti, Pascal; Charafe-Jauffret, Emmanuelle; Chaffanet, Max; Restouin, Audrey; Marchetto, Sylvie; Collette, Yves; Gonçalvès, Anthony; Macara, Ian; Birnbaum, Daniel; Kodjabachian, Laurent; Johansen, Terje; Borg, Jean-Paul (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-01-12)
      The non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour ...
    • Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses 

      Tusco, Radu; Jacomin, Anne-Claire; Jain, Ashish; Penman, Bridget S.; Larsen, Kenneth Bowitz; Johansen, Terje; Nezis, Ioannis P. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-02)
      Selective autophagy is a catabolic process with which cellular material is specifically targeted for degradation by lysosomes. The function of selective autophagic degradation of self-components in the regulation of innate immunity is still unclear. Here we show that Drosophila Kenny, the homolog of mammalian IKKγ, is a selective autophagy receptor that mediates the degradation of the IκB kinase ...
    • Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma 

      Pölonen, Petri; Jawahar Deen, Ashik; Leinonen, Hanna M.; Jyrkkänen, Henna-Kaisa; Kuosmanen, Suvi; Mononen, Mimmi; Jain, Ashish; Tuomainen, Tomi; Pasonen-Seppänen, Sanna; Hartikainen, Jaana M.; Mannermaa, Arto; Nykter, Matti; Tavi, Pasi; Johansen, Terje; Heinäniemi, Merja; Levonen, Anna-Liisa (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-23)
      Accumulating evidence suggests that constitutively active Nrf2 has a pivotal role in cancer as it induces pro-survival genes that promote cancer cell proliferation and chemoresistance. The mechanisms of Nrf2 dysregulation and functions in cancer have not been fully characterized. Here, we jointly analyzed the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Atlas (TCGA) ...
    • P62/sequestosome-1, autophagy-related gene 8, and autophagy in Drosophila are regulated by nuclear factor erythroid 2-related factor 2(NRF2), independent of transcription factor TFEB 

      Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja Sandra; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-04-30)
      The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads ...
    • Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation 

      Kumar, Suresh; Gu, Yuexi; Abudu, Yakubu Princely; Bruun, Jack-Ansgar; Jain, Ashish; Farzam, Farzin; Mudd, Michal H.; Anonsen, Jan Haug; Rusten, Tor Erik; Kasof, Gary; Ktistakis, Nicholas; Lidke, Keith A; Johansen, Terje; Deretic, Vojo (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-28)
      Syntaxin 17 (Stx17) has been implicated in autophagosome-lysosome fusion. Here, we report that Stx17 functions in assembly of protein complexes during autophagy initiation. Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13<sup>+</sup>FIP200<sup>+</sup> mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 ...
    • Phosphorylation of the LIR Domain of SCOC Modulates ATG8 Binding Affinity and Specificity 

      Wirth, Martina; Mouilleron, Stephane; Zhang, Wenxin; Abudu, Yakubu Princely; Jain, Ashish; Olsvik, Hallvard Lauritz; Bruun, Jack-Ansgar; Razi, Minoo; Jefferies, Harold B.J.; Lee, Rebecca; Joshi, Dhira; O'Reilly, Nicola; Johansen, Terje; Tooze, Sharon A (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-24)
      <p>Autophagy is a highly conserved degradative pathway, essential for cellular homeostasis and implicated in diseases including cancer and neurodegeneration. Autophagy-related 8 (ATG8) proteins play a central role in autophagosome formation and selective delivery of cytoplasmic cargo to lysosomes by recruiting autophagy adaptors and receptors. The LC3-interacting region (LIR) docking site (LDS) of ...
    • Regulation of Expression of Autophagy Genes by Atg8a-Interacting Partners Sequoia, YL-1, and Sir2 in Drosophila 

      Jacomin, Anne-Claire; Petridi, Stavroula; Di Monaco, Marisa; Bhujabal, Zambarlal; Jain, Ashish; Mulakkal, Nitha C.; Palara, Anthimi; Powell, Emma L.; Chung, Bonita; Zampronio, Cleidiane; Jones, Alexandra; Cameron, Alexander; Johansen, Terje; Nezis, Ioannis P. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-26)
      Autophagy is the degradation of cytoplasmic material through the lysosomal pathway. One of the most studied autophagy-related proteins is LC3. Despite growing evidence that LC3 is enriched in the nucleus, its nuclear role is poorly understood. Here, we show that <i>Drosophila</i> Atg8a protein, homologous to mammalian LC3, interacts with the transcription factor Sequoia in a LIR motif-dependent ...
    • TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1 

      Overå, Katrine Stange; Garcia-Garcia, Juncal; Bhujabal, Zambarlal; Jain, Ashish; Larsen, Kenneth Bowitz; Deretic, Vojo; Johansen, Terje; Lamark, Trond; Sjøttem, Eva (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-02)
      The tripartite motif (TRIM) proteins constitute a family of ubiquitin E3 ligases involved in a multitude of cellular processes, including protein homeostasis and autophagy. TRIM32 is characterized by six protein–protein interaction domains termed NHL, various point mutations in which are associated with limb-girdle-muscular dystrophy 2H (LGMD2H). Here, we show that TRIM32 is an autophagy substrate. ...