Wagner Mary J, Helbing Caren C
Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, Victoria, BC, Canada V8W 3P6.
Gen Comp Endocrinol. 2005 Oct;144(1):38-50. doi: 10.1016/j.ygcen.2005.04.008.
The tumor suppressor candidate, inhibitor of growth (ING) is implicated in the control of apoptosis, cell cycle progression, chemosensitivity, and senescence. There are at least five different genes in mammals, ING1-ING5, and there is limited evidence that multiple transcript variants exist for ING1 that encode proteins with different functions. No variants have yet been reported for other ING genes. Here, we report the isolation of seven Xenopus laevis (x)ING1 and three xING2 transcript variants and give the first evidence for their independent regulation by thyroid hormone (TH). Comparison with mammalian genes reveals conservation in gene structure. xING1 and xING2 transcript variants are differentially expressed in adult tissues with the greatest number of variants expressed at high levels in brain, testis, and eye. During metamorphosis of the tadpole into a frog, the hindlimb, tail, and brain undergo growth, apoptosis, or remodeling, respectively. We show that xING1 and xING2 transcript variants are significantly reduced in the hindlimb while many variants increase in the tail. These transcript variants remain largely unchanged in the brain during this developmental period. By exposing premetamorphic tadpoles to TH, a precocious metamorphosis is induced. We identify specific variants whose steady state levels are significantly affected by TH at 24 and 48h of exposure. Although several of the variants show expression patterns reminiscent of that observed in natural metamorphosis, the results indicate that additional factors may be involved to influence the steady state transcript levels during development.
肿瘤抑制候选基因生长抑制因子（ING）与细胞凋亡、细胞周期进程、化学敏感性和衰老的调控有关。哺乳动物中至少有五个不同的基因，即ING1 - ING5，仅有有限的证据表明ING1存在多种转录变体，这些变体编码具有不同功能的蛋白质。尚未有关于其他ING基因变体的报道。在此，我们报告了非洲爪蟾（x）ING1的七个转录变体和xING2的三个转录变体的分离，并首次提供了它们受甲状腺激素（TH）独立调控的证据。与哺乳动物基因的比较揭示了基因结构的保守性。xING1和xING2转录变体在成年组织中差异表达，其中在脑、睾丸和眼中表达的变体数量最多且表达水平较高。在蝌蚪变态发育成青蛙的过程中，后肢、尾巴和大脑分别经历生长、凋亡或重塑。我们发现xING1和xING2转录变体在后肢中显著减少，而在尾巴中有许多变体增加。在这个发育阶段，这些转录变体在大脑中基本保持不变。通过将变态前的蝌蚪暴露于TH，可诱导早熟变态。我们鉴定出在暴露24小时和48小时时其稳态水平受TH显著影响的特定变体。尽管有几个变体的表达模式让人联想到在自然变态中观察到的模式，但结果表明在发育过程中可能涉及其他因素来影响稳态转录水平。
