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

doi:10.1074/jbc.m115.656116

Cited by 62 publications

(64 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5C). Several of the proteins or their mammalian homologs, including GAR1 (probable H/ACA ribonucleoprotein complex subunit), GSTT3 (glutathione S-transferase D3), PSA5 (proteasome subunit a type-5), TMEDE (transmembrane emp24 domain-containing protein eca), REF2P [protein ref (2)P], CP391 (probable CYP309a1), and ENOPH (enolase-phosphatase E1), that were identified in the Furin1-knockdown fat bodies have been associated with stress responses (52)(53)(54)(55)(56). For example, the human homolog for TMEDE/eca (i.e., TMED4 or ERS25) is induced by endoplasmic reticulum-specific stress, heat shock, and oxidative stress (54).…”

Section: Comparison Of the Morphology Of The Fat Body And Proteomes Omentioning

confidence: 99%

Proprotein convertaseFurin1expression in theDrosophilafat body is essential for a normal antimicrobial peptide response and bacterial host defense

et al. 2017

View full text Add to dashboard Cite

Invading pathogens provoke robust innate immune responses in Dipteran insects, such as In a systemic bacterial infection, a humoral response is induced in the fat body. Gram-positive bacteria trigger the Toll signaling pathway, whereas gram-negative bacterial infections are signaled the immune deficiency (IMD) pathway. We show here that the RNA interference-mediated silencing of -a member of the proprotein convertase enzyme family-specifically in the fat body, results in a reduction in the expression of antimicrobial peptides. This, in turn, compromises the survival of adult fruit flies in systemic infections that are caused by both gram-positive and -negative bacteria. plays a nonredundant role in the regulation of immune responses, as silencing of , the other member of the enzyme family, had no effect on survival or the expression of antimicrobial peptides upon a systemic infection. does not directly affect the Toll or IMD signaling pathways, but the reduced expression of up-regulates stress response factors in the fat body. We also demonstrate that is a negative regulator of the Janus kinase/signal transducer and activator of transcription signaling pathway, which is implicated in stress responses in the fly. In summary, our data identify as a novel regulator of humoral immunity and cellular stress responses in-Aittomäki, S., Valanne, S., Lehtinen, T., Matikainen, S., Nyman, T. A., Rämet, M., Pesu, M. Proprotein convertase expression in the fat body is essential for a normal antimicrobial peptide response and bacterial host defense.

show abstract

Section: Comparison Of the Morphology Of The Fat Body And Proteomes Omentioning

confidence: 99%

Proprotein convertaseFurin1expression in theDrosophilafat body is essential for a normal antimicrobial peptide response and bacterial host defense

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This process enhances the positive-feedback loop resulting from Nrf2-mediated activation of p62 gene expression [24]. Keap1 in the complex with phosphorylated p62 is degraded by selective autophagy [24][25][26], contributing to the shutdown of this pathway. In this p62-Keap1-Nrf2 pathway, Nrf2 is activated even in the absence of Keap1 modification [21,23].…”

mentioning

confidence: 99%

p62/SQSTM1 functions as a signaling hub and an autophagy adaptor

2015

View full text Add to dashboard Cite

and ichimura-ys@med.niigata-u.ac.jp p62/SQSTM1 is a stress-inducible cellular protein that is conserved among metazoans 20 but not in plants and fungi. p62/SQSTM1 has multiple domains that mediate its interactions with various binding partners, and it serves as a signaling hub for diverse cellular events such as amino-acid sensing and the oxidative stress response. In addition, p62/SQSTM1 functions as a selective autophagy receptor for degradation of ubiqutinated substrates. Herein we delineate the current knowledge about p62 with regard to mTORC1 25 activation, the Keap1-Nrf2 pathway, and selective autophagy.

show abstract

“…Moreover, DmKEAP1 can directly interact with Atg8 (homologue to mammalian LC3). KEAP1 deficiency results in Atg8 and autophagy induction dependent on the NRF2 orthologue CncC and independent on TFEB/MITF [106]. The relationship between NRF2 and autophagy seems to be conserved though, highlighting its functional relevance.…”

Section: Functional Connection Between Nrf2 and Macroautophagymentioning

confidence: 99%

Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases

2017

View full text Add to dashboard Cite

Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2). NRF2 has been classically considered as the master regulator of the antioxidant cell response, although it is currently emerging as a key component of the transduction machinery to maintain proteostasis. As we will discuss, NRF2 could be envisioned as a hub that compiles emergency signals derived from misfolded protein accumulation in order to build a coordinated and perdurable transcriptional response. This is achieved by functions of NRF2 related to the control of genes involved in the maintenance of the endoplasmic reticulum physiology, the proteasome and autophagy.

show abstract

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

Cited by 62 publications

References 79 publications

Proprotein convertaseFurin1expression in theDrosophilafat body is essential for a normal antimicrobial peptide response and bacterial host defense

Proprotein convertaseFurin1expression in theDrosophilafat body is essential for a normal antimicrobial peptide response and bacterial host defense

p62/SQSTM1 functions as a signaling hub and an autophagy adaptor

Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases

Contact Info

Product

Resources

About