RASSF1A Inactivation Unleashes a Tumor Suppressor/Oncogene Cascade with Context-Dependent Consequences on Cell Cycle Progression.
AuthorsRam RR, Mendiratta S, Bodemann BO, Torres MJ, Eskiocak U, White MA,
Journal
PubMed ID24732797
'The RASSF1A gene is one of the most frequently inactivated genes in over 30 different types of cancers (H. Donninger, M. D. Vos, and G. J. Clark, J. Cell Sci. 120:3163-3172, 2007, http://dx.doi.org/10.1242/jcs.010389). Despite the prevalence of RASSF1A silencing in human cancer, the mechanism by which RASSF1A functions as a ... More
Tuberin binds p27 and negatively regulates its interaction with the SCF component Skp2.
AuthorsRosner M, Hengstschläger M,
JournalJ Biol Chem
PubMed ID15355997
TSC1 (tuberous sclerosis complex 1) encoding hamartin and TSC2 encoding tuberin are tumor suppressor genes responsible for the autosomal dominantly inherited disease tuberous sclerosis. These genes have been demonstrated to negatively regulate cell cycle progression, the activity of cdk2, and the degradation of the cyclin-dependent kinase inhibitor p27. To date, ... 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
Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy.
Decreased p27(Kip1) levels are a poor prognostic factor in many malignancies, and can occur through up-regulation of SCF(Skp2) E3 ligase function, resulting in enhanced p27 ubiquitination and proteasome-mediated degradation. While proteasome inhibitors stabilize p27(Kip1), agents inhibiting SCF(Skp2) may represent more directly targeted drugs with the promise of enhanced efficacy and ... More