Dataset Information

Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.

ABSTRACT: In Caenorhabditis elegans, ROS generated in response to intestinal infection induces SKN-1, a protective transcription factor homologous to nuclear factor erythroid 2-related factor 1 or 2 (NRF1/2) in mammals. Many factors regulate SKN-1, including the p38 mitogen-activated protein kinase (MAPK) cascade that activates SKN-1 by phosphorylation. In this work, another positive regulator of SKN-1 is identified: NIPI-3, a Tribbles pseudokinase. NIPI-3 has been reported to protect against intestinal infection by negatively regulating the CCAT enhancer binding protein (C/EBP) bZIP transcription factor CEBP-1. Here we demonstrate that CEBP-1 positively regulates the vhp-1 transcript, which encodes a phosphatase that dephosphorylates the p38 MAPK called PMK-1. The increased levels of VHP-1 caused by CEBP-1 transcriptional enhancement result in less PMK-1 phosphorylation, affecting SKN-1 activity and intestinal resistance to the pathogen. The data support a model in which NIPI-3's negative regulation of CEBP-1 decreases VHP-1 phosphatase activity, allowing increased stimulation of SKN-1 activity by the p38 MAPK phosphorylation cascade in the intestine.

SUBMITTER: Wu C

PROVIDER: S-EPMC8393239 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.

Wu Chenggang C Karakuzu Ozgur O Garsin Danielle A DA

Cell reports 20210801 7

In Caenorhabditis elegans, ROS generated in response to intestinal infection induces SKN-1, a protective transcription factor homologous to nuclear factor erythroid 2-related factor 1 or 2 (NRF1/2) in mammals. Many factors regulate SKN-1, including the p38 mitogen-activated protein kinase (MAPK) cascade that activates SKN-1 by phosphorylation. In this work, another positive regulator of SKN-1 is identified: NIPI-3, a Tribbles pseudokinase. NIPI-3 has been reported to protect against intestinal i ...[more]

PMID: 34407394

Similar Datasets

Project description:Members of the Tribbles (TRIB) family of pseudokinases are critical components of intracellular signal transduction pathways in physiological and pathological processes. TRIBs, including TRIB2, have been previously shown as signaling mediators and scaffolding proteins regulating numerous cellular events such as proliferation, differentiation and cell death through protein stability and activity. However, the signaling network associated with TRIB2 and its binding partners in granulosa cells during ovarian follicular development is not fully defined. We previously reported that TRIB2 is differentially expressed in growing dominant follicles while downregulated in ovulatory follicles following the luteinizing hormone (LH) surge or human chorionic gonadotropin (hCG) injection. In the present study, we used the yeast two-hybrid screening system and in vitro coimmunoprecipitation assays to identify and confirm TRIB2 interactions in granulosa cells (GCs) of dominant ovarian follicles (DFs), which yielded individual candidate binding partners including calmodulin 1 (CALM1), inhibin subunit beta A (INHBA), inositol polyphosphate phosphatase-like 1 (INPPL1), 5'-nucleotidase ecto (NT5E), stearoyl-CoA desaturase (SCD), succinate dehydrogenase complex iron sulfur subunit B (SDHB) and Ras-associated protein 14 (RAB14). Further analyses showed that all TRIB2 binding partners are expressed in GCs of dominant follicles but are differentially regulated throughout the different stages of follicular development. CRISPR/Cas9-driven inhibition along with pQE-driven overexpression of TRIB2 showed that TRIB2 differently regulates expression of binding partners, which reveals the importance of TRIB2 in the control of gene expression linked to various biological processes such as proliferation, differentiation, cell migration, apoptosis, calcium signaling and metabolism. These data provide a larger view of potential TRIB2-regulated signal transduction pathways in GCs and provide strong evidence that TRIB2 may act as a regulator of target genes during ovarian follicular development.

Dataset Information

Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.

Publications

Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets