Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation
| Autor: | Indu Jose Thoompumkal, Kumaraswamy Anbarasu, Krishnan Rehna, Sundarasamy Mahalingam |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell signaling Leucine zipper Transcription Genetic Down-Regulation Apoptosis GTPase Biology Models Biological 03 medical and health sciences 0302 clinical medicine GTP-Binding Proteins Cell Line Tumor Report Humans Protein Interaction Domains and Motifs Phosphorylation Nuclear protein Molecular Biology Cell Proliferation Protein Stability Cell growth Tumor Suppressor Proteins NF-kappa B Transcription Factor RelA Nuclear Proteins Cell Biology NFKB1 Molecular biology Cell biology Gene Expression Regulation Neoplastic HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Ectopic expression Signal transduction Protein Binding Signal Transduction Developmental Biology |
| Zdroj: | Cell Cycle. 15:3251-3267 |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | Guanine nucleotide binding protein-like 3-like (GNL3L) is an evolutionarily conserved putative nucleolar GTPase belonging to the HSR1-MMR1 family. In the present study, using protein-protein interaction assays, we show that Leucine Zipper Down-regulated in Cancer-1 (LDOC1) is a novel interacting partner of GNL3L. Furthermore, our results reveal that ectopic expression of LDOC1 destabilizes endogenous GNL3L levels and down modulates GNL3L-induced cell proliferation, in contrast, the knockdown of LDOC1 potentiates cell proliferation upon GNL3L expression. Interestingly, GNL3L upregulates NF-κB dependent transcriptional activity by modulating the expression of NF-κB subunit p65, which is reversed upon co-expression of LDOC1 with GNL3L. GNL3L also potentiates TNF-α mediated NF-κB activity. In addition, anti-apoptotic function of GNL3L is impaired upon p65 knockdown, suggesting its critical role in GNL3L mediated cell proliferation/survival. An inverse correlation of GNL3L and LDOC1 expression profiles in various tumor tissues from BioXpress database indicate their critical role in cancer. Collectively, our data provides evidence that GNL3L-LDOC1 interplay regulates cell proliferation through the modulation of NF-κB pathway during tumorigenesis. |
| Databáze: | OpenAIRE |
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