English
norskBlar i forfatter "Abudu, Yakubu Princely"
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Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-18)Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill‐defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3‐interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8‐SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate ... -
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 ... -
NIPSNAP1 and NIPSNAP2 Act as “Eat Me” Signals for Mitophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-11)The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog ... -
Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation
(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
(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 ... -
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 ... -
SAMM50 is a receptor for basal piecemeal mitophagy and acts with SQSTM1/p62 in OXPHOS-induced mitophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-18)Mitophagy, the clearance of surplus or damaged mitochondria or mitochondrial parts by autophagy, is important for maintenance of cellular homeostasis. Whereas knowledge on programmed and stress-induced mitophagy is increasing, much less is known about mechanisms of basal mitophagy. Recently, we identified SAMM50 (SAMM50 sorting and assembly machinery component) as a receptor for piecemeal degradation ... -
SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-05)The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective ... -
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 ... -
TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1
(Journal article; Tidsskriftartikkel, 2022-12-27)Limitation of excessive inflammation due to selective degradation of pro-inflammatory proteins is one of the cytoprotective functions attributed to autophagy. In the current study, we highlight that selective autophagy also plays a vital role in promoting the establishment of a robust inflammatory response. Under inflammatory conditions, here TLR3-activation by poly(I:C) treatment, the inflammation ... -
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 ...
