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
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Cancer-1 中亮氨酸拉链下调 (LDOC1) 与鸟嘌呤核苷酸结合蛋白样 3 样 (GNL3L) 相互作用，在细胞增殖过程中调节核因子 -κ B (NF-κB) 信号传导
作者：
Indu Jose Thoompumkal;K. Rehna;K. Anbarasu;S. Mahalingam
鸟嘌呤核苷酸结合蛋白样3样蛋白（GNL 3L）是一种进化上保守的核仁GT3蛋白，属于HSR 1-MMR 1家族。在本研究中，使用蛋白质-蛋白质相互作用测定，我们表明，亮氨酸拉链下调的癌症-1（LDOC 1）是一种新的相互作用伴侣的GNL 3L。此外，我们的研究结果表明，LDOC 1的异位表达不稳定的内源性GNL 3L水平和下调GNL 3L诱导的细胞增殖，相比之下，LDOC 1的敲低增强GNL 3L表达后的细胞增殖。有趣的是，GNL 3 L通过调节NF-κB亚基p65的表达上调NF-κB依赖性转录活性，这在LDOC 1与GNL 3 L共表达时逆转。GNL 3 L还增强TNF-α介导的NF-κB活性。此外，GNL 3L的抗凋亡功能在p65敲低后受损，表明其在GNL 3L介导的细胞增殖/存活中的关键作用。来自BioXpress数据库的各种肿瘤组织中GNL 3L和LDOC 1表达谱的负相关性表明它们在癌症中的关键作用。总的来说，我们的数据提供了证据表明，GNL 3 L-LDOC 1相互作用通过调节NF-κB通路在肿瘤发生过程中调节细胞增殖。
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.
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影响因子：
56.9
作者：
Wang, CY;Mayo, MW;Baldwin, AS
通讯作者：
Baldwin, AS
系统性红斑狼疮患者 T 淋巴细胞中 NF-κ B 活性异常与 p65-RelA 蛋白表达降低相关。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Wong,HK;Kammer,GM;Dennis,G;Tsokos,GC
通讯作者：
Tsokos,GC
影响因子：
11.4
作者：
Duckett, CS;Nava, VE;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
2.9
作者：
Dyer, BW;Ferrer, FA;Rodriguez, R
通讯作者：
Rodriguez, R