LDOC1, a novel MZF‐1‐interacting protein, induces apoptosis

Inoue, Masatoshi; Takahashi, Kyôko; Niide, Osamu; Shibata, Masahiko; Fukuzawa, Masahiro; Ra, Chisei

doi:10.1016/j.febslet.2004.12.030

Cited by 44 publications

(43 citation statements)

References 17 publications

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“…23,25,26 The observed downregulation of GNL3L by LDOC1 may significantly influence cell proliferation and apoptosis in mammalian cells. Recent reports suggest that LDOC1 is a novel regulator of NF-kB activity 23 and GNL3L acts as a mediator of NF-kB pathway, 27 but the mechanism remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2016

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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-kB dependent transcriptional activity by modulating the expression of NF-kB subunit p65, which is reversed upon coexpression of LDOC1 with GNL3L. GNL3L also potentiates TNF-a mediated NF-kB activity. In addition, antiapoptotic 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 NFkB pathway during tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

“…23,25,26 In order to define the effect of LDOC1 on GNL3L function during cell proliferation, we performed various in vitro functional assays. Flag-GNL3L and LDOC1-HA were transiently expressed in HEK293T cells and the rate of cell proliferation was analyzed using MTT assay.…”

Section: Ldoc1 Inhibits Gnl3l Functionmentioning

confidence: 99%

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

et al. 2016

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“…SPANX-C TAR clones also contain another gene, LDOC1, which has been shown to be down-regulated in some cancers (Nagasaki et al 1999;Inoue et al 2005). To investigate whether X-linked patients have mutational changes in this gene, ∼1.2-kb promoter and coding sequences were PCR amplified from TAR isolates (Supplemental Table 1S) and sequenced.…”

Section: Analysis Of Ldoc1 Did Not Reveal Any Mutations In the Codingmentioning

confidence: 99%

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Kouprina¹,

Pavlı́ček²,

Noskov

et al. 2005

Genome Res.

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Genetic linkage studies indicate that germline variations in a gene or genes on chromosome Xq27-28 are implicated in prostate carcinogenesis. The linkage peak of prostate cancer overlies a region of ∼750 kb containing five SPANX genes (SPANX-A1, -A2, -B, -C, and -D) encoding sperm proteins associated with the nucleus; their expression was also detected in a variety of cancers. SPANX genes are >95% identical and reside within large segmental duplications (SDs) with a high level of similarity, which confounds mutational analysis of this gene family by routine PCR methods. In this work, we applied transformation-associated recombination cloning (TAR) in yeast to characterize individual SPANX genes from prostate cancer patients showing linkage to Xq27-28 and unaffected controls. Analysis of genomic TAR clones revealed a dynamic nature of the replicated region of linkage. Both frequent gene deletion/duplication and homology-based sequence transfer events were identified within the region and were presumably caused by recombinational interactions between SDs harboring the SPANX genes. These interactions contribute to diversity of the SPANX coding regions in humans. We speculate that the predisposition to prostate cancer in X-linked families is an example of a genomic disease caused by a specific architecture of the SPANX gene cluster.

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“…LDOC-1 is a known regulator of the nuclear factor (NF)-κB-mediated pathway of apoptosis through the inhibition of NF-κB (12). The expression of Wiskott-Aldrich syndrome protein family, member 3 induces the translocation of LDOC-1 from the nucleus to the cytoplasm, resulting in the inhibition of LDOC1-induced apoptosis (22,23). In addition, the transcription factor myeloid zinc finger gene 1 was demonstrated to interact with LDOC-1 and to enhance the activity of LDOC-1, thus favoring apoptosis (22,23).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of Wiskott-Aldrich syndrome protein family, member 3 induces the translocation of LDOC-1 from the nucleus to the cytoplasm, resulting in the inhibition of LDOC1-induced apoptosis (22,23). In addition, the transcription factor myeloid zinc finger gene 1 was demonstrated to interact with LDOC-1 and to enhance the activity of LDOC-1, thus favoring apoptosis (22,23). Recently, Buchholtz et al (24) observed a low expression of LDOC-1 in ovarian cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

et al. 2016

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Abstract. Numerous genetic alterations have been implicated in the development of prostate cancer (PCa). DNA and protein microarrays have enabled the identification of genes associated with apoptosis, which is important in PCa development. Despite the molecular mechanisms are not entirely understood, inhibition of apoptosis is a critical pathophysiological factor that contributes to the onset and progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a known regulator of the nuclear factor (NF)-mediated pathway of apoptosis through the inhibition of NF-κB. The present study investigated the expression of the LDOC-1 gene in LNCaP, PC-3, PNT1A and PNT2 prostate cell lines by reverse transcription-quantitative polymerase chain reaction. In addition LDOC-1 protein expression in normal prostate tissues and PCa was studied by immunohistochemistry. LDOC-1 messenger RNA resulted overexpressed in LNCaP and PC-3 PCa cell lines compared with the two normal prostate cell lines PNT1A and PNT2. The results of immunohistochemistry demonstrated a positive cytoplasmic LDOC-1 staining in all PCa and normal prostate samples, whereas no nuclear staining was observed in any sample. Furthermore, a more intense signal was evidenced in PCa samples. LDOC-1 gene overexpression in PCa suggests an activity of LDOC-1 in PCa cell lines.

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LDOC1, a novel MZF‐1‐interacting protein, induces apoptosis

Cited by 44 publications

References 17 publications

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

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

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

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