Related Experiment Video

Updated: May 21, 2025

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

428

Peli1, regulated by m6A modification, suppresses NLRP3 inflammasome activation in atherosclerosis by inhibiting YB-1

Qiang Liu1,2, Lu Yan1, Tao Wu1

  • 1Department of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Communications Biology
|March 19, 2025
PubMed

Insights

Pellino 1 (Peli1) suppresses atherosclerosis by targeting Y-box binding protein 1 (YB-1). Peli1 promotes YB-1 degradation, inhibiting NLRP3 inflammasome activation and AS progression.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • The NLRP3 inflammasome in macrophages accelerates atherosclerosis (AS) progression.
  • Understanding regulators of NLRP3 inflammasome activation in AS is crucial.

Purpose of the Study:

  • To investigate the role of Pellino 1 (Peli1) in regulating NLRP3 inflammasome activation during AS development.
  • To elucidate the molecular mechanisms by which Peli1 influences AS progression.

Main Methods:

  • In vivo and in vitro studies using YB-1 knockdown and Peli1 manipulation.
  • Assessment of lipid accumulation and inflammation in macrophages.
  • Investigation of ubiquitination, N6-methyladenosine (m6A) modification, and mRNA degradation pathways.

Main Results:

  • YB-1 knockdown inhibited AS progression, reducing ox-LDL-induced lipid accumulation and inflammation by inactivating NLRP3 inflammasome.
  • Peli1 mediated ubiquitination-dependent degradation of YB-1.
  • YTHDC2 recognized METTL3-mediated Peli1 m6A modification, leading to Peli1 mRNA degradation.
  • YB-1 upregulation counteracted the protective effects of Peli1 upregulation on AS.

Conclusions:

  • Peli1, regulated by m6A modification, suppresses AS progression.
  • Peli1 inhibits YB-1-mediated NLRP3 inflammasome activation in macrophages via promoting YB-1 ubiquitination.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

8.7K
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.4K

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.1K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
862
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.8K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K