English
norskBlar i forfatter "Larsen, Kenneth Bowitz"
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ATG8 Family Proteins Act as Scaffolds for Assembly of the ULK Complex SEQUENCE REQUIREMENTS FOR LC3-INTERACTING REGION (LIR) MOTIFS
(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 ... -
CALCOCO1 acts with VAMP ‐associated proteins to mediate ER ‐phagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-11)The endoplasmic reticulum (ER) plays important roles in protein synthesis and folding, and calcium storage. The volume of the ER and expression of its resident proteins are increased in response to nutrient stress. ER‐phagy, a selective form of autophagy, is involved in the degradation of the excess components of the ER to restore homeostasis. Six ER‐resident proteins have been identified as ER‐phagy ... -
The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-28)The long non-coding RNA <i>NEAT1</i> locus is transcribed into two overlapping isoforms, <i>NEAT1_1</i> and <i>NEAT1_2</i>, of which the latter is essential for the assembly of nuclear paraspeckles. <i>NEAT1</i> is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown ... -
The FMRpolyGlycine protein mediates aggregate formation and toxicity independent of the CGG mRNA hairpin in a cellular model for FXTAS
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-28)Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG-repeat expansion in the 5′ UTR of the FMR1 gene on the X-chromosome. Both elevated levels of the expanded FMR1 mRNA and aberrant expression of a polyglycine protein (FMRpolyG) from the CGG-repeat region are hypothesized to trigger the pathogenesis of FXTAS. While increased expression of FMRpolyG leads ... -
FYCO1 contains a C-terminally extended, LC3A/B-preferring LC3-interacting region (LIR) motif required for efficient maturation of autophagosomes during basal autophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-10-14)FYCO1 (FYVE and coiled-coil protein 1) is a transport adaptor that binds to phosphatidylinositol 3-phosphate, to Rab7, and to LC3 (microtubule-associated protein 1 light chain 3) to mediate transport of late endosomes and autophagosomes along microtubules in the plus end direction. We have previously shown that FYCO1 binds to LC3B via a 19-amino acid sequence containing a putative core LC3-interacting ... -
High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-07-05)Mitochondria are susceptible to damage resulting from their activity as energy providers. Damaged mitochondria can cause harm to the cell and thus mitochondria are subjected to elaborate quality-control mechanisms including elimination via lysosomal degradation in a process termed mitophagy. Basal mitophagy is a house-keeping mechanism fine-tuning the number of mitochondria according to the metabolic ... -
Hypo-osmotic stress induces the epithelial alarmin IL-33 in the colonic barrier of ulcerative colitis
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-07)Epithelial alarmins are gaining interest as therapeutic targets for chronic infammation. The nuclear alarmin interleukin-33 (IL-33) is upregulated in the colonic mucosa of acute ulcerative colitis (UC) and may represent an early instigator of the infammatory cascade. However, it is not clear what signals drive the expression of IL-33 in the colonic mucosa, nor is the exact role of IL-33 elucidated. We ... -
Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
(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 ... -
NIMA-related kinase 9–mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-19)Human ATG8 family proteins (ATG8s) are active in all steps of the macroautophagy pathway, and their lipidation is essential for autophagosome formation. Lipidated ATG8s anchored to the outer surface of the phagophore serve as scaffolds for binding of other core autophagy proteins and various effector proteins involved in trafficking or fusion events, whereas those at the inner surface are needed for ... -
Regulation of Golgi turnover by CALCOCO1-mediated selective autophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-19)The Golgi complex is essential for the processing, sorting, and trafficking of newly synthesized proteins and lipids. Golgi turnover is regulated to meet different cellular physiological demands. The role of autophagy in the turnover of Golgi, however, has not been clarified. Here we show that CALCOCO1 binds the Golgi-resident palmitoyltransferase ZDHHC17 to facilitate Golgi degradation by autophagy ... -
SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-26)Mitophagy is the degradation of surplus or damaged mitochondria by autophagy. In addition to programmed and stress-induced mitophagy, basal mitophagy processes exert organelle quality control. Here, we show that the sorting and assembly machinery (SAM) complex protein SAMM50 interacts directly with ATG8 family proteins and p62/SQSTM1 to act as a receptor for a basal mitophagy of components of the ... -
Starvation induces rapid degradation of selective autophagy receptors by endosomal microautophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2018-07-17)It is not clear to what extent starvation-induced autophagy affects the proteome on a global scale and whether it is selective. In this study, we report based on quantitative proteomics that cells during the first 4 h of acute starvation elicit lysosomal degradation of up to 2–3% of the proteome. The most significant changes are caused by an immediate autophagic response elicited by shortage of amino ... -
Transforming growth factor-beta-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs
(Journal article; Tidsskriftartikkel; Peer reviewed, 2011)The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKC?/? and PKC? serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel ... -
TRIM27 is an autophagy substrate facilitating mitochondria clustering and mitophagy via phosphorylated TBK1
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-09-16)Tripartite motif-containing protein 27 (TRIM27/also called RFP) is a multifunctional ubiquitin E3 ligase involved in numerous cellular functions, such as proliferation, apoptosis, regulation of the NF-kB pathway, endosomal recycling and the innate immune response. TRIM27 interacts directly with TANK-binding kinase 1 (TBK1) and regulates its stability. TBK1 in complex with autophagy receptors is ... -
TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1
(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. ...
