| First Author | Li Z | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 8 | Pages | 2961-2969 |
| PubMed ID | 30643022 | Mgi Jnum | J:275340 |
| Mgi Id | MGI:6304638 | Doi | 10.1074/jbc.AC118.006041 |
| Citation | Li Z, et al. (2019) A novel thyroid hormone receptor isoform, TRbeta2-46, promotes SKP2 expression and retinoblastoma cell proliferation. J Biol Chem 294(8):2961-2969 |
| abstractText | Retinoblastoma is a childhood retinal tumor that develops from cone photoreceptor precursors in response to inactivating RB1 mutations and loss of functional RB protein. The cone precursor's response to RB loss involves cell type-specific signaling circuitry that helps to drive tumorigenesis. One component of the cone precursor circuitry, the thyroid hormone receptor beta2 (TRbeta2), enables the aberrant proliferation of diverse RB-deficient cells in part by opposing the down-regulation of S-phase kinase-associated protein 2 (SKP2) by the more widely expressed and tumor-suppressive TRbeta1. However, it is unclear how TRbeta2 opposes TRbeta1 to enable SKP2 expression and cell proliferation. Here, we show that in human retinoblastoma cells TRbeta2 mRNA encodes two TRbeta2 protein isoforms: a predominantly cytoplasmic 54-kDa protein (TRbeta2-54) corresponding to the well-characterized full-length murine Trbeta2 and an N-terminally truncated and exclusively cytoplasmic 46-kDa protein (TRbeta2-46) that starts at Met-79. Whereas TRbeta2 knockdown decreased SKP2 expression and impaired retinoblastoma cell cycle progression, re-expression of TRbeta2-46 but not TRbeta2-54 stabilized SKP2 and restored proliferation to an extent similar to that of ectopic SKP2 restoration. We conclude that TRbeta2-46 is an oncogenic thyroid hormone receptor isoform that promotes SKP2 expression and SKP2-dependent retinoblastoma cell proliferation. |
