Document Detail


Depletion of K-Ras promotes proteasome degradation of survivin.
MedLine Citation:
PMID:  23324341     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutant K-Ras and survivin both contribute to oncogenesis, but little is known about K-Ras requirement for the maintenance of the high levels of survivin in human tumors. Here we demonstrate that K-Ras depletion significantly decreases survivin levels in human cancer cells that harbor mutant but not wild type K-Ras. K-Ras depletion attenuates both basal and drug-induced survivin levels. The mechanism by which K-Ras depletion decreases survivin levels is through ubiquitination and proteasomal degradation of survivin and is independent of survivin-Thr-34 phosphorylation. Depletion of RalA and RalB, but not Raf-1, Akt1 and Akt2, decreases survivin levels, suggesting that K-Ras may regulate survivin stability through its RalGDS/Ral but not PI3K/Akt and Raf-1/Mek effector pathways. Furthermore, the ability of mutant K-Ras to induce anchorage-independent growth, invasion and survival is compromised by depletion of survivin. These studies suggest that mutant K-Ras contributes to the maintenance of the aberrantly high levels of survivin in tumors by regulating its stability, and that the ability of mutant K-Ras to induce malignant transformation is, at least in part, dependent on these high levels of survivin.
Authors:
Awet Tecleab; Saïd M Sebti
Publication Detail:
Type:  Journal Article     Date:  2013-01-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  12     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-11     Completed Date:  2013-08-01     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  522-32     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Cell Line
Cell Proliferation
Cell Survival
HEK293 Cells
Humans
Inhibitor of Apoptosis Proteins / genetics,  metabolism*
Mice
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Proteasome Endopeptidase Complex / metabolism
Proto-Oncogene Proteins c-akt / genetics,  metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Proto-Oncogene Proteins p21(ras) / deficiency,  genetics*,  metabolism*
RNA Interference
RNA, Small Interfering
Signal Transduction / genetics
Ubiquitination
raf Kinases / genetics,  metabolism
ral GTP-Binding Proteins / genetics,  metabolism
ral Guanine Nucleotide Exchange Factor / metabolism
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Ralb protein, human; 0/ral Guanine Nucleotide Exchange Factor; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/AKT2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/raf Kinases; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 3.6.1.-/RALA protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras); EC 3.6.5.2/ral GTP-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  New epigenetic pathway for stemness maintenance mediated by the histone methyltransferase Ezh1.
Next Document:  P-TEFb as a target to reactivate latent HIV: Two Brds are now in hand.