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首页> 外文期刊>Oncogene >Fusion proteins of retinoid receptors antagonize TGF-|[beta]|-induced growth inhibition of lung epithelial cells
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Fusion proteins of retinoid receptors antagonize TGF-|[beta]|-induced growth inhibition of lung epithelial cells

机译：类维生素A受体的融合蛋白拮抗TGF- |β|诱导的肺上皮细胞生长抑制

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Transforming growth factor-1 (TGF-) is a growth factor that has multiple functions including potent inhibition of cell growth. TGF- signals by binding to its cell surface serine/threonine kinase receptors, which in turn phosphorylate downstream signal transducers, Smad2 and Smad3. Phosphorylated Smad2 and Smad3, together with Smad4, enter the nucleus and associate with various transcription factors. This complex of transcription factors regulates transcription of a diverse group of genes, leading to growth arrest at G1 phase. Through a functional expression cloning approach, a gag–retinoid X receptor (gag–RXR) fusion protein was found to antagonize TGF--induced growth inhibition of mink lung epithelial cells and the fusion between gag and RXR is essential for resistance to the growth inhibition. Like gag–RXR, the oncogenic PLZF–RAR fusion protein also antagonizes TGF--induced growth inhibition, and the fusion between PLZF and RAR is essential for resistance to TGF-. Moreover, TGF- and retinoic acid (RA) cooperatively induce growth inhibition as well as transcription of the p15ink4b gene, while PLZF–RAR represses TGF--induced expression of the p15ink4b gene. Together, these results suggest that the TGF- and RA pathways cooperate to inhibit cell growth and that PLZF–RAR -mediated resistance to TGF- may facilitate the development of the PLZF–RAR-induced leukemia.
机译：转化生长因子-1（TGF-）是一种具有多种功能的生长因子，包括有效抑制细胞生长。 TGF-通过与细胞表面的丝氨酸/苏氨酸激酶受体结合而发出信号，从而使下游信号转导子Smad2和Smad3磷酸化。磷酸化的Smad2和Smad3与Smad4一起进入细胞核并与各种转录因子相关。转录因子的这种复合物调节多种基因的转录，从而导致G1期的生长停滞。通过功能性表达克隆方法，发现gag-类视黄醇X受体（gag-RXR）融合蛋白可拮抗TGF诱导的水貂肺上皮细胞的生长抑制，而gag和RXR之间的融合对于抵抗生长抑制至关重要。像gag–RXR一样，致癌的PLZF–RAR融合蛋白也拮抗TGF-诱导的生长抑制，并且PLZF和RAR之间的融合对于抵抗TGF-至关重要。此外，TGF和视黄酸（RA）协同诱导生长抑制以及p15ink4b基因的转录，而PLZF–RAR抑制TGF诱导的p15ink4b基因的表达。总之，这些结果表明，TGF-和RA途径协同抑制细胞生长，PLZF-RAR介导的对TGF-的抗性可能促进PLZF-RAR诱导的白血病的发展。

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