title: 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.
abstract: 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.
authors.affiliation: a Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology , Indian Institute of Technology-Madras , Chennai , India.
authors.forename: Indu Jose
authors.initials: IJ
authors.lastname: Thoompumkal
authors.affiliation: a Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology , Indian Institute of Technology-Madras , Chennai , India.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Rehna
authors.affiliation: a Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology , Indian Institute of Technology-Madras , Chennai , India.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Anbarasu
authors.affiliation: a Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology , Indian Institute of Technology-Madras , Chennai , India.
authors.forename: Sundarasamy
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C509155:GNL3L protein, human; C120625:LDOC1 protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D025521:Tumor Suppressor Proteins; D019204:GTP-Binding Proteins
keywords: Apoptosis; GNL3L; LDOC1; NF-κB transcription factor; cell signaling; proliferation; protein-protein interaction