Two “Edges” in Our Knowledge on the Functions of Ribosomal Proteins: The Revealed Contributions of Their Regions to Translation Mechanisms and the Issues of Their Extracellular Transport by Exosomes

Ochkasova, Anastasia S.; Arbuzov, Grigory; Malygin, Alexey A.; Graifer, D. M.

doi:10.3390/ijms241411458

Cited by 5 publications

References 110 publications

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SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

Balakrishnan

Adnani

Chinchalongporn

et al. 2020

Preprint

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Oligodendrogliomas are lower-grade, slow-growing gliomas that are ultimately fatal. Although driver mutations are known, the mechanisms underlying their signature slow growth rates are poorly understood. We found evidence for intra-tumoral interactions between neoplastic and nonneoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived oligodendroglioma cell lines of lower and higher aggressivity. Both oligodendroglioma cell lines released extracellular vesicles that had cytotoxic effects on nonneoplastic and neoplastic cells, but each had distinct vesicular proteomes. Consistent with extracellular vesicles mediating growth inhibitory effects in oligodendrogliomas, higher expression levels of several extracellular vesicle biogenesis genes (SMPD3,TSG101, STAM1) correlates with longer survival in oligodendroglioma patients. Furthermore, SMPD3 overexpression slows oligodendroglioma cell growth in culture. Conversely, SMPD3 knockdown enhances oligodendroglioma proliferation in vitro, in murine xenografts, and in human cerebral organoid co-cultures. Oligodendroglioma-derived extracellular vesicles thus mediate tumor cell microenvironmental interactions that contribute to low aggressivity.

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SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

Balakrishnan

Adnani

Chinchalongporn

et al. 2020

Preprint

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Multi-omics profiling reveals dysregulated ribosome biogenesis and impaired cell proliferation following knockout of CDR2L

Solheim,

Gerking,

Kråkenes

et al. 2024

BMC Cancer

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Background Cerebellar degeneration-related (CDR) proteins are associated with paraneoplastic cerebellar degeneration (PCD) – a rare, neurodegenerative disease caused by tumour-induced autoimmunity against neural antigens resulting in degeneration of Purkinje neurons in the cerebellum. The pathogenesis of PCD is unknown, in large part due to our limited understanding of the functions of CDR proteins. To this end, we performed an extensive, multi-omics analysis of CDR-knockout cells focusing on the CDR2L protein, to gain a deeper understanding of the properties of the CDR proteins in ovarian cancer. Methods Ovarian cancer cell lines lacking either CDR1, CDR2, or CDR2L were analysed using RNA sequencing and mass spectrometry-based proteomics to assess changes to the transcriptome, proteome and secretome in the absence of these proteins. Results For each knockout cell line, we identified sets of differentially expressed genes and proteins. CDR2L-knockout cells displayed a distinct expression profile compared to CDR1- and CDR2-knockout cells. Knockout of CDR2L caused dysregulation of genes involved in ribosome biogenesis, protein translation, and cell cycle progression, ultimately causing impaired cell proliferation in vitro. Several of these genes showed a concurrent upregulation at the transcript level and downregulation at the protein level. Conclusions Our study provides the first integrative multi-omics analysis of the impact of knockout of the CDR genes, providing both new insights into the biological properties of the CDR proteins in ovarian cancer, and a valuable resource for future investigations into the CDR proteins.

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CRABP1-complexes in exosome secretion

Nhieu,

Wei,

Ludwig

et al. 2024

Cell Commun Signal

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Background Cellular retinoic acid binding protein 1 (CRABP1) mediates rapid, non-canonical activity of retinoic acid (RA) by forming signalosomes via protein-protein interactions. Two signalosomes have been identified previously: CRABP1-MAPK and CRABP1-CaMKII. Crabp1 knockout (CKO) mice exhibited altered exosome profiles, but the mechanism of CRABP1 action was unclear. This study aimed to screen for and identify novel CRABP1 signalosomes that could modulate exosome secretion by using a combinatorial approach involving biochemical, bioinformatic and molecular studies. Methods Immunoprecipitation coupled with mass spectrometry (IP-MS) identified candidate CRABP1-interacting proteins which were subsequently analyzed using GO Term Enrichment, Functional Annotation Clustering; and Pathway Analysis. Gene expression analysis of CKO samples revealed altered expression of genes related to exosome biogenesis and secretion. The effect of CRABP1 on exosome secretion was then experimentally validated using CKO mice and a Crabp1 knockdown P19 cell line. Results IP-MS identified CRABP1-interacting targets. Bioinformatic analyses revealed significant association with actin cytoskeletal dynamics, kinases, and exosome secretion. The effect of CRABP1 on exosome secretion was experimentally validated by comparing circulating exosome numbers of CKO and wild type (WT) mice, and secreted exosomes from WT and siCRABP1-P19 cells. Pathway analysis identified kinase signaling and Arp2/3 complex as the major pathways where CRABP1-signalosomes modulate exosome secretion, which was validated in the P19 system. Conclusion The combinatorial approach allowed efficient screening for and identification of novel CRABP1-signalosomes. The results uncovered a novel function of CRABP1 in modulating exosome secretion, and suggested that CRABP1 could play roles in modulating intercellular communication and signal propagation.

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Two “Edges” in Our Knowledge on the Functions of Ribosomal Proteins: The Revealed Contributions of Their Regions to Translation Mechanisms and the Issues of Their Extracellular Transport by Exosomes

Cited by 5 publications

References 110 publications

SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

Multi-omics profiling reveals dysregulated ribosome biogenesis and impaired cell proliferation following knockout of CDR2L

CRABP1-complexes in exosome secretion

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