Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein

Solomon-Zemler, Ravid; Pozniak, Yair; Geiger, Tamar; Werner, Haim

doi:10.1016/j.ymgme.2019.01.002

Cited by 8 publications

(8 citation statements)

References 28 publications

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“…Recent mass spectrometry (MS)-based proteomic analyses, designed to identify nuclear IGF1R interactors, allowed us to detect a series of novel proteins that have not been previously linked to the IGF1 signaling pathway [47] (Table 1). Briefly, experiments consisted of immunoprecipitation of the nuclear fractions of benign MCF10A breast cells using an IGF1R antibody, followed by MS analysis of candidate interactors.…”

Section: Is Nuclear Insr/igf1r Translocation Limited To Malignant Cells?mentioning

confidence: 99%

The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer

2021

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Insulin (InsR) and insulin-like growth factor-1 (IGF1R) receptors mediate the metabolic and growth-promoting actions of insulin and IGF1/IGF2, respectively. Evidence accumulated in recent years indicates that, in addition to their typical cell-surface localization pattern and ligand-activated mechanism of action, InsR and IGF1R are present in the cell nucleus of both normal and transformed cells. Nuclear translocation seems to involve interaction with a small, ubiquitin-like modifier protein (SUMO-1), although this modification is not always a prerequisite. Nuclear InsR and IGF1R exhibit a number of biological activities that classically fit within the definition of transcription factors. These nuclear activities include, among others, sequence-specific DNA binding and transcriptional control. Of particular interest, nuclear IGF1R was capable of binding and stimulating its cognate gene promoter. The physiological relevance of this autoregulatory mechanism needs to be further investigated. In addition to its nuclear localization, studies have identified IGF1R in the Golgi apparatus, and this particular distribution correlated with a migratory phenotype. In summary, the newly described roles of InsR and IGF1R as gene regulators, in concert with their atypical pattern of subcellular distribution, add a further layer of complexity to traditional models of cell signaling. Furthermore, and in view of the emerging role of IGF1R as a potential therapeutic target, a better understanding of the mechanisms responsible for nuclear IGF1R transport and identification of IGF1R interactors might help optimize target directed therapies in oncology.

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Section: Is Nuclear Insr/igf1r Translocation Limited To Malignant Cells?mentioning

confidence: 99%

The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer

2021

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“…NOM1 (nucleolar protein with MIF4G domain 1) is a member of the MIF4G/MA3 family identified at the chromosome 7q36 breakpoint involved in processes that impact translation [88]. Solomon-Zemler et al [89] reported that NOM1 has biological pathways associated with nuclear IGF1R (insulin-like growth factor-1 receptor), and inhibition of nuclear IGF1R translocation by dansylcadaverine reduced NOM1 levels in nuclei of MCF7 cells. According to Gunawardena et al [90], NOM1 is a PP1 (protein phosphatase I) nucleolar targeting subunit, which is an essential eukaryotic serine/threonine phosphatase required for many cellular processes, including cell division, signaling, and metabolism.…”

Section: Candidate Gene Identificationmentioning

confidence: 99%

Genome-Wide Association Study Reveals Candidate Genes for Litter Size Traits in Pelibuey Sheep

Hernández-Montiel

Martínez-Núñez

Ramón-Ugalde

et al. 2020

Animals

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The Pelibuey sheep has adaptability to climatic variations, resistance to parasites, and good maternal ability, whereas some ewes present multiple births, which increases the litter size in farm sheep. The litter size in some wool sheep breeds is associated with the presence of mutations, mainly in the family of the transforming growth factor β (TGF-β) genes. To explore genetic mechanisms underlying the variation in litter size, we conducted a genome-wide association study in two groups of Pelibuey sheep (multiparous sheep with two lambs per birth vs. uniparous sheep with a single lamb at birth) using the OvineSNP50 BeadChip. We identified a total of 57 putative SNPs markers (p < 3.0 × 10−3, Bonferroni correction). The candidate genes that may be associated with litter size in Pelibuey sheep are CLSTN2, MTMR2, DLG1, CGA, ABCG5, TRPM6, and HTR1E. Genomic regions were also identified that contain three quantitative trait loci (QTLs) for aseasonal reproduction (ASREP), milk yield (MY), and body weight (BW). These results allowed us to identify SNPs associated with genes that could be involved in the reproductive process related to prolificacy.

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“…One plausible strategy includes the use of combination therapy, for which an in-depth understanding of nIGF1R function is essential. Although nIGF1R is known for its various functions in cell growth and proliferation, as well as metastasis and DSB repair (13,17,25,(41)(42)(43), understanding of the regulatory mechanisms remains limited. In the present study, proteomics and global network analyses were performed to identify the functional partners of nIGF1R in colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nuclear IGF1R interacts with NuMA and regulates 53BP1‑dependent DNA double‑strand break repair in colorectal cancer

Zhang

Segar

et al. 2021

Oncol Rep

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Nuclear insulin-like growth factor 1 receptor (nIGF1R) has been associated with poor overall survival and chemotherapy resistance in various types of cancer; however, the underlying mechanism remains unclear. In the present study, immunoprecipitation-coupled mass spectrometry was performed in an IGF1R-overexpressing SW480-OE colorectal cancer cell line to identify the nIGF1R interactome. Network analysis revealed 197 proteins of interest which were involved in several biological pathways, including RNA processing, DNA double-strand break (DSB) repair and SUMOylation pathways. Nuclear mitotic apparatus protein (NuMA) was identified as one of nIGF1R's colocalizing partners. Proximity ligation assay (PLA) revealed different levels of p53-binding protein 1 (53BP1)-NuMA colocalization between IGF1R-positive (R + ) and IGF1R-negative (R -) mouse embryonic fibroblasts following exposure to ionizing radiation (IR). 53BP1 was retained by NuMA in the Rcells during IR-induced DNA damage. By contrast, the level of NuMA-53BP1 was markedly lower in R + cells compared with Rcells. The present data suggested a regulatory role of nIGF1R in 53BP1-dependent DSB repair through its interaction with NuMA. Bright-field PLA analysis on a paraffin-embedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA-53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1-dependent DDR by regulating the NuMA-53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.

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Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein

Cited by 8 publications

References 28 publications

The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer

The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer

Genome-Wide Association Study Reveals Candidate Genes for Litter Size Traits in Pelibuey Sheep

Nuclear IGF1R interacts with NuMA and regulates 53BP1‑dependent DNA double‑strand break repair in colorectal cancer

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