Multiple variants of the ING1 and ING2 tumor suppressors are differentially expressed and thyroid hormone-responsive in Xenopus laevis

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 48 h 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.