| First Author | Rosner M | Year | 2007 |
| Journal | Hum Mol Genet | Volume | 16 |
| Issue | 13 | Pages | 1541-56 |
| PubMed ID | 17470459 | Mgi Jnum | J:125107 |
| Mgi Id | MGI:3723553 | Doi | 10.1093/hmg/ddm103 |
| Citation | Rosner M, et al. (2007) p27Kip1 localization depends on the tumor suppressor protein tuberin. Hum Mol Genet 16(13):1541-56 |
| abstractText | p27(Kip1) plays an important role in cell cycle regulation by inhibiting cyclin-CDK complex activity in the nucleus. p27(Kip1) is regulated by its concentration as well as by its subcellular localization. Tuberin, encoded by the tuberous sclerosis tumor suppressor gene TSC2, is a potent negative cell cycle regulator. We show herein, that tuberin induces nuclear p27 localization by inhibiting its 14-3-3-mediated cytoplasmic retention. Tuberin interferes with 14-3-3's counteracting effects on p27-mediated cell cycle arrest. Akt-mediated phosphorylation of p27, but not of tuberin, negatively regulates tuberin's potential to trigger p27 nuclear localization. In G0 cells, tuberin binds p27 triggering downregulation of p27's binding to 14-3-3 and of its cytoplasmic retention. At transition to S phase p27 is phosphorylated by Akt, tuberin/p27 complex levels are downregulated and binding of p27 to 14-3-3 increases triggering cytoplasmic retention of p27. These findings demonstrate p27 localization during the mammalian cell cycle to be under the control of the tumor suppressor tuberin. |
