| 2016 |
IER5 forms a ternary complex with HSF1 and PP2A, and promotes PP2A-dependent dephosphorylation of HSF1 at multiple serine and threonine residues, generating a novel hypo-phosphorylated active form of HSF1 that is transcriptionally active and contributes to cancer cell proliferation under stress. |
Co-immunoprecipitation, Western blot (dephosphorylation assay), overexpression and knockdown in cancer cell lines |
Scientific reports |
High |
26754925
|
| 2015 |
IER5 interacts with PP2A and its B55 regulatory subunits; expression of IER5 and B55 leads to HSF1 dephosphorylation and activation of HSF1 target genes. B55 subunits directly bind HSF1, and IER5 functions as a positive feedback regulator of HSF1 through PP2A/B55. |
Co-immunoprecipitation, gene expression assays (HSF1 target genes), overexpression studies |
FEBS letters |
High |
25816751
|
| 2015 |
IER5 physically interacts with PP2A B55 regulatory subunit (via N-terminal region), with ribosomal protein S6 kinase (S6K), and with HSF1; these interactions are essential for reduced phosphorylation of both S6K and HSF1. IER5 oligomerizes via its N-terminal region, and oligomeric IER5 regulates PP2A activity and cell growth. |
Deletion analysis, co-immunoprecipitation, Western blot (phosphorylation assays), cell growth assays |
FEBS letters |
High |
26496226
|
| 2025 |
Cryo-EM structure of PP2A/B55α in complex with the N-terminal structured region of IER5 (IER5-N50) shows that IER5-N50 occludes the substrate-recruitment surface on B55α. IER5-N50 inhibits PP2A/B55α-catalyzed dephosphorylation of pTau in biochemical assays. Mutations disrupting the PP2A/B55α interface of full-length IER5 abrogate co-immunoprecipitation of PP2A/B55α and suppress KRT1 expression in keratinocytes. Structural bioinformatics identified homology of IER5-N50 with SERTA domain-containing proteins. |
Cryo-EM structure determination, in vitro biochemical dephosphorylation assay, mutagenesis, co-immunoprecipitation, IER5 knockout cells with rescue experiments |
Cell chemical biology |
High |
40209703
|
| 2020 |
IER5 is a direct Notch target gene required for Notch-induced squamous cell differentiation. IER5 is epistatic to PPP2R2A (encoding PP2A B55α subunit), and IER5 interacts with B55α both in cells and in purified systems, placing IER5 downstream of Notch and upstream of PP2A/B55α in a differentiation pathway. |
Conditional Notch activation, siRNA knockdown, genetic epistasis (IER5 vs PPP2R2A), co-immunoprecipitation in cells and with purified proteins |
eLife |
High |
32936072
|
| 2019 |
IER5 contains a classical bipartite nuclear localization signal (NLS) at amino acids 217–244, conserved across species, that mediates complex formation with importin-α and importin-β. An intact NLS is essential for HSF1 dephosphorylation and full HSF1 activation by IER5. |
NLS deletion/mutation analysis, co-immunoprecipitation with importin-α/β, HSF1 dephosphorylation assay, subcellular localization experiments |
Experimental cell research |
High |
31669744
|
| 2022 |
IER5 acts as a PP2A adapter protein that binds both the B55 regulatory subunit of PP2A and the target proteins RB and RB-like 1 (p107/RBL1), enhancing PP2A-catalyzed dephosphorylation of these proteins and repressing expression of various cell cycle-related genes. |
Co-immunoprecipitation, knockdown, Western blot (phosphorylation), ChIP (RB promoter binding), gene expression analysis |
The FEBS journal |
High |
36047562
|
| 2025 |
IER5 functions as a positive regulator of p53 by inhibiting p53 ubiquitination and increasing cellular p53 levels. Mechanistically, IER5-PP2A/B55 complex dephosphorylates MDM2 at Ser166, leading to MDM2 ubiquitination and reduction of nuclear MDM2, thereby stabilizing p53. This requires IER5 nuclear localization and binding to both PP2A/B55 and MDM2. |
Co-immunoprecipitation (IER5-MDM2), ubiquitination assay, Western blot (p53, MDM2 phosphorylation), MDM2 inhibitor (Nutlin-3) experiment, nuclear localization mutants |
Cellular signalling |
High |
40081547
|
| 2011 |
IER5 overexpression inhibits AML progenitor cell proliferation through G2/M arrest and transcriptional repression of Cdc25B. IER5 directly binds the Cdc25B promoter and mediates transcriptional attenuation through NF-YB and p300 transcription factors. |
Overexpression in AML cell lines, ChIP (IER5 binding to Cdc25B promoter), colony formation assay, flow cytometry (cell cycle), rescue experiment with Cdc25B overexpression |
PloS one |
Medium |
22132193
|
| 2021 |
After irradiation, IER5 binds to the Cdc25B promoter and causes release of the coactivator p300 through interaction with NF-YB, transcriptionally repressing Cdc25B expression. Both Sp1/Sp3 and NF-YB binding sites on the Cdc25B promoter are involved in irradiation-mediated regulation. |
Dual-luciferase reporter assay, site-directed mutagenesis of promoter elements, ChIP assay (IER5, NF-YB, p300 at Cdc25B promoter), IER5 siRNA knockdown |
Toxicology research |
Medium |
34484679
|
| 2014 |
IER5 expression is induced by heat shock in an HSF1-dependent manner; the IER5 promoter contains an HSF1 binding sequence that is occupied by heat-activated HSF1. Overexpression of IER5 upregulates chaperone gene expression, increases refolding of heat-denatured proteins, and helps cells recover viability after heat challenge, establishing a positive feedback loop between HSF1 and IER5. |
HSF1-dependent promoter analysis, ChIP (HSF1 binding to IER5 promoter), IER5 overexpression, protein refolding assay, cell viability assay after heat shock |
The FEBS journal |
Medium |
25355627
|
| 2017 |
IER5 participates in non-homologous end-joining (NHEJ) repair of DNA double-strand breaks. IER5 physically interacts with PARP1 and Ku70, as confirmed by immunoprecipitation. IER5 knockdown significantly decreased efficiency of DSB repair. PARP1 inhibitor Olaparib affected IER5 stability. |
siRNA knockdown (DSB repair efficiency assay), mass spectrometry (interactome), immunoprecipitation (IER5-PARP1, IER5-Ku70), pharmacological inhibition (Olaparib) |
International journal of medical sciences |
Medium |
29104487
|
| 2009 |
siRNA-mediated suppression of IER5 in HeLa cells increased cell proliferation, enhanced radioresistance (at doses up to 6 Gy), and potentiated radiation-induced G2/M arrest while increasing the fraction of S-phase cells, demonstrating that IER5 affects radiosensitivity via modulation of radiation-induced cell cycle checkpoints. |
siRNA knockdown, cell growth assay, colony survival assay, flow cytometry (cell cycle analysis) |
Radiation and environmental biophysics |
Medium |
19238419
|
| 2016 |
GCF (GC binding factor) negatively regulates IER5 transcription by binding to two GCF binding sites in the IER5 promoter; mutations of these sites increased luciferase activity. Radiation reduced GCF-DNA complex formation at the IER5 promoter in a dose-dependent manner, contributing to radiation-induced IER5 upregulation. |
Luciferase reporter assay, site-directed mutagenesis of promoter GCF sites, ChIP, electrophoretic mobility shift assay (EMSA) |
Cancer gene therapy |
Medium |
26915404
|
| 2020 |
PAF1 inhibits IER5 transcription by promoting RNA Pol II pausing at the IER5 promoter-proximal region, primarily through binding to IER5 enhancers. PAF1 knockdown increases IER5 expression and radiosensitivity; simultaneous PAF1 and IER5 knockdown abolishes this effect, placing PAF1 upstream of IER5 in regulating radiosensitivity. |
siRNA knockdown, ChIP, CRISPR/Cas9 enhancer knockout, qRT-PCR, flow cytometry (apoptosis), CCK-8 assay |
Radiation oncology (London, England) |
Medium |
32471508
|
| 1999 |
IER5 encodes a 308-amino-acid, highly proline-rich nuclear protein with homology to the N-terminus of IER2/pip92/ETR101. It contains a PEST-like sequence (suggesting rapid degradation), multiple phosphorylation sites, and is induced by serum and growth factors with slow-kinetics immediate-early gene characteristics. Unlike pip92/IER2, IER5 induction does not require protein kinase C activity. |
Molecular cloning, sequence analysis, Northern blot, promoter sequence analysis, PKC inhibitor experiments |
Genomics |
Medium |
10049588
|