The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2).
AuthorsTedesco D, Lukas J, Reed SI,
JournalGenes Dev
PubMed ID12435635
'p130 is a tumor suppressor of the pocket protein family whose expression is posttranscriptionally regulated and largely G0 restricted. The mechanism of down-regulation of p130 expression in proliferating cells was investigated. Our results indicate that the decline of p130 expression as G0 cells reenter the cell cycle is due to ... More
Inhibition of F-Box protein p45(SKP2) expression and stabilization of cyclin-dependent kinase inhibitor p27(KIP1) in vitamin D analog-treated cancer cells.
AuthorsLin R, Wang TT, Miller WH, White JH,
JournalEndocrinology
PubMed ID12586749
'Treatment of cancer cells with 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)] or its analogs induces growth arrest and expression of the cyclin-dependent kinase inhibitor p27(KIP1). Although 1,25(OH)(2)D(3) transiently enhances p27(kip1) gene transcription in some cells, its effects on p27(KIP1) protein levels are generally more gradual and sustained. This suggests that 1,25(OH)(2)D(3) treatment may ... More
Ubiquitination and proteolysis of cancer-derived Smad4 mutants by SCFSkp2.
AuthorsLiang M, Liang YY, Wrighton K, Ungermannova D, Wang XP, Brunicardi FC, Liu X, Feng XH, Lin X,
JournalMol Cell Biol
PubMed ID15314162
Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-beta) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, ... More