ArticleThe Journal of biological chemistry2013
Nuclear ALG-2 protein interacts with Ca2+ homeostasis endoplasmic reticulum protein (CHERP) Ca2+-dependently and participates in regulation of alternative splicing of inositol trisphosphate receptor type 1 (IP3R1) pre-mRNA.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Integrating transcriptomics and hybrid machine learning enables high-accuracy diagnostic modeling for nasopharyngeal carcinoma.Discover oncology · 2025Article
- High-throughput identification of calcium-regulated proteins across diverse proteomes.Cell reports · 2024Article
- High-Throughput Identification of Calcium Regulated Proteins Across Diverse Proteomes.bioRxiv : the preprint server for biology · 2024Article
- Article
- CHERP Regulates the Alternative Splicing of pre-mRNAs in the Nucleus.International journal of molecular sciences · 2022Article
- Evidence for complex dynamics during U2 snRNP selection of the intron branchpoint.Nucleic acids research · 2021Article
- The influence of environmental calcium on the branchial morphology in a catadromous fish.Environmental science and pollution research international · 2021Article
- Tyramide signal amplification mass spectrometry (TSA-MS) ratio identifies nuclear speckle proteins.The Journal of cell biology · 2020Article
- The Penta-EF-Hand ALG-2 Protein Interacts with the Cytosolic Domain of the SOCE Regulator SARAF and Interferes with Ubiquitination.International journal of molecular sciences · 2020Article
- PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.Journal of experimental & clinical cancer research : CR · 2020Article
- Taurine AttenuatesFrontiers in immunology · 2019Article
- Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-Palindromic NFAT-Response Elements Facilitates Analysis of Biological Endpoint Effects of Cellular CaInternational journal of molecular sciences · 2018Article
- The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins.The Journal of biological chemistry · 2017Article
- Down-regulation of CHERP inhibits neuroblastoma cell proliferation and induces apoptosis through ER stress induction.Oncotarget · 2017Article
- Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking.International journal of molecular sciences · 2016Review
- Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins.Nucleic acids research · 2015Article
- Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2.International journal of molecular sciences · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular Ca(2+) signaling pathway is important for the control of broad cellular processes from fertilization to cell death. ALG-2 is a Ca(2+)-binding protein that contains five serially repeated EF-hand motifs and interacts with various proteins in a Ca(2+)-dependent manner. Although ALG-2 is present both in the cytoplasm and in the nucleus, little is known about its nuclear function. Ca(2+) homeostasis endoplasmic reticulum protein (CHERP) was first identified as an endoplasmic reticulum protein that regulates intracellular Ca(2+) mobilization in human cells, but recent proteomics data suggest an association between CHERP and spliceosomes. Here, we report that CHERP, containing a Pro-rich region and a phosphorylated Ser/Arg-rich RS-like domain, is a novel Ca(2+)-dependent ALG-2-interactive target in the nucleus. Immunofluorescence microscopic analysis revealed localization of CHERP to the nucleoplasm with prominent accumulation at nuclear speckles, which are the sites of storage and modification for pre-mRNA splicing factors. Live cell time-lapse imaging showed that nuclear ALG-2 was recruited to the CHERP-localizing speckles upon Ca(2+) mobilization. Results of co-immunoprecipitation assays revealed binding of CHERP to a phosphorylated form of RNA polymerase II. Knockdown of CHERP or ALG-2 in HT1080 cells resulted in generation of alternatively spliced isoforms of the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) pre-mRNA that included exons 41 and 42 in addition to the major isoform lacking exons 40-42. Furthermore, binding between CHERP and IP3R1 RNA was detected by an RNA immunoprecipitation assay using a polyclonal antibody against CHERP. These results indicate that CHERP and ALG-2 participate in regulation of alternative splicing of IP3R1 pre-mRNA and provide new insights into post-transcriptional regulation of splicing variants in Ca(2+) signaling pathways.
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