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HSPA13 facilitates NF-κB–mediated transcription and attenuates cell death responses in TNFα signaling
- Source :
- Science Advances
- Publication Year :
- 2021
- Publisher :
- American Association for the Advancement of Science (AAAS), 2021.
-
Abstract
- Description<br />HSPA13 is a novel checkpoint regulator in the TNFα signaling pathway controlling cellular physiological outcomes.<br />RIP1 has emerged as a master regulator in TNFα signaling that controls two distinct cellular fates: cell survival versus programmed cell death. Because the default response of most cells to TNFα is NF-κB–mediated inflammation and survival, a specific mechanism must exist to control the divergence of signaling outcome. Here, we identify HSPA13 as a transcription-independent checkpoint to modulate the role of RIP1 in TNFα signaling. Through specific binding to TNFR1 and RIP1, HSPA13 enhances TNFα-induced recruitment of RIP1 to TNFR1, and consequently promotes downstream NF-κB transcriptional responses. Meanwhile, HSPA13 attenuates the participation of RIP1 in cytosolic complex II and prevents cells from programmed death. Loss of HSPA13 shifts the transition of RIP1 from complex I to complex II and promotes both apoptosis and necroptosis. Thus, our study provides compelling evidence for the cellular protective function of HSPA13 in fine-tuning TNFα responses.
- Subjects :
- Programmed cell death
Multidisciplinary
Chemistry
Necroptosis
SciAdv r-articles
Inflammation
NF-κB
Cell Biology
Cell biology
Cytosol
chemistry.chemical_compound
Apoptosis
Transcription (biology)
medicine
Tumor necrosis factor alpha
Biomedicine and Life Sciences
medicine.symptom
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi.dedup.....52eaa7734d98f3c361d88b4c283138af