STAT1 Represses Skp2 Gene Transcription to Promote p27 Stabilization in Ras-Transformed Cells
نویسندگان
چکیده
Authors' A Mortimer Experimen Medicine, M Correspon Medical Re 508, 3999 1E2. Phon antonis.kor Medical Re 508, 3999 1E2. Phon swang@ldi.
منابع مشابه
STAT1 represses Skp2 gene transcription to promote p27Kip1 stabilization in Ras-transformed cells.
The S-phase kinase-associated protein 2 (Skp2) is an F-box protein that serves as a subunit of the Skp1-Cullin-F-box ubiquitin protein ligase complex. Skp2 is overexpressed in many tumors and promotes tumor formation through its ability to induce the degradation of proteins with antiproliferative and tumor-suppressor functions, such as p27(Kip1). The signal transducer and activator of transcrip...
متن کاملStat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1
Inactivation of p27 Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an inte...
متن کاملOncogenic Ras blocks transforming growth factor-beta-induced cell-cycle arrest by degradation of p27 through a MEK/Erk/SKP2-dependent pathway.
OBJECTIVE To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS Two leukemic cell lines bearing N-Ras(L61) mutations; HL-60 and TF-1, and the M1 cell line with wt Ras were investiga...
متن کاملAbsence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease.
BCR-ABL is proposed to impair cell-cycle control by disabling p27, a tumor suppressor that inhibits cyclin-dependent kinases. We show that in cell lines p27 expression is inversely correlated with expression of SKP2, the F-box protein of SCF(SKP2) (SKP1/Cul1/F-box), the E3 ubiquitin ligase that promotes proteasomal degradation of p27. Inhibition of BCR-ABL kinase causes G(1) arrest, down-regula...
متن کاملProdigiosin down-regulates SKP2 to induce p27(KIP1) stabilization and antiproliferation in human lung adenocarcinoma cells.
BACKGROUND AND PURPOSE High levels of SKP2 are a poor prognostic factor in multiple human cancers and mostly correlate with low p27(KIP1) levels. Prodigiosin is a bacterial tripyrrole pigment with strong pro-apoptotic activity. Induction of cell cycle blockade underlies one of its anticancer actions but the mechanisms involved are unclear. The aim of this study was to explore the role of the SK...
متن کامل