The subcellular locations of pl5(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2 Journal Article
| Authors: | Reynisdóttir, I.; Massagué, J. |
| Article Title: | The subcellular locations of pl5(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2 |
| Abstract: | In dividing cells, p27(Kip1) is predominantly bound to cyclin D-cdk4 without inhibiting this kinase. Upon being induced by TGF-β or with a conditional expression system in lung epithelial cells, p15(Ink4b) binds to and inhibits the cyclin D-dependent kinases, prevents p27 binding to these cdk complexes, and promotes p27 binding and inhibition of cyclin-cdk2. In vitro, however, p15 prevents p27 binding only if it has access to cyclin D- cdk4 first. We present evidence that the different subcellular location of p15 and p27 ensures the prior access of p15 to cdk4. In the cell, p15 is localized mostly in the cytoplasm, whereas p27 is nuclear. p15 prevails over p27 or a p27 construct consisting of the cdk inhibitory domain tagged with a nuclear localization signal. However, when p15 and p27 are forced to reside in the same subcellular location, either the cytoplasm or the nucleus, p15 no longer prevents p27 from binding to cdk4. These properties allow p15 and p27 to coordinately inhibit cdk4 and cdk2. |
| Keywords: | carrier protein; oncoprotein; promoter region; proto-oncogene proteins; protein analysis; cell cycle protein; animal; metabolism; animals; cell cycle proteins; cell division; enzyme inhibition; cell line; protein binding; protein serine threonine kinase; drug antagonism; protein-serine-threonine kinases; cyclin dependent kinase inhibitor 1b; mammal; carrier proteins; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; cellular distribution; cell fractionation; cyclin-dependent kinase inhibitor p16; cyclin d1; tumor suppressor protein; cyclin-dependent kinases; cyclin dependent kinase; subcellular fractions; cyclin dependent kinase 4; cyclin-dependent kinase 4; mink; cdk inhibitors; cyclin dependent kinase 2; cyclin-dependent kinase 2; cyclin-dependent kinase inhibitor p15; microtubule-associated proteins; microtubule associated protein; cyclin dependent kinase inhibitor 2b; cdk2 protein, human; tandem repeat; p27(kip1); lung alveolus epithelium; protein p16ink4a; cdc2-cdc28 kinases; cdk4 protein, human; humans; human; priority journal; article; cdkn2b protein, human; cyclin d-cdk4/6; p151(ink4b); subcellular location |
| Journal Title: | Genes and Development |
| Volume: | 11 |
| Issue: | 4 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 1997-02-15 |
| Start Page: | 492 |
| End Page: | 503 |
| Language: | English |
| PUBMED: | 9042862 |
| PROVIDER: | scopus |
| DOI: | 10.1101/gad.11.4.492 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
