Premium
Proteomic profiling in distinct cellular compartments of tumor cells reveals p53‐dependent upregulation of S100A6 upon induction of telomere dysfunction
Author(s) -
Zimmermann Stefan,
Biniossek Martin L.,
Maurer Christian,
Münzer Patrick,
Pantic Milena,
Veelken Hendrik,
Martens Uwe M.
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200900232
Subject(s) - telomerase , telomere , biology , downregulation and upregulation , proteome , proteomics , dna damage , microbiology and biotechnology , cell culture , senescence , telomerase reverse transcriptase , ribonucleoprotein , cell growth , cancer research , rna , dna , gene , genetics
Telomere dysfunction is evoking a DNA damage response which leads to replicative senescence or apoptosis. Tumor cells feature telomerase, a ribonucleoprotein complex counteracting telomere shortening and proliferation limitation as a prerequisite of immortal cell growth. Recently, we demonstrated the effects of telomerase inhibition on the proteome of tumor cell clones in whole cell lysates by SELDI‐TOF‐MS profiling and MS/MS protein identification (Zimmermann et al. , Proteomics 2009, 9 , 521–534). We continued proteomic analyses of such clones after telomerase‐inhibition using fractionation of cellular compartments. Among the differentially expressed peaks found in different fractions, a cytoplasmic 10.1 kDa protein upregulated in telomerase‐inhibited clones ( p <0.0001) was identified by nanoflow‐HPLC‐MS/MS as S100A6. S100A6 upregulation was confirmed by immunoblotting in telomerase‐inhibited HCT‐116, A‐549, and NCI‐H460 clones. S100A6 and other proteins involved in telomere dysfunction were further analyzed in derivative p53 −/− and p21 −/− HCT‐116 cell lines indicating an overall reduced number of significant changes in these lines compared to wild type HCT‐116 cells. In addition, post‐translational modification of S100A6 was demonstrated with a potential role in mediating the cellular response to telomere dysfunction. In conclusion, proteomic profiling in distinct cellular compartments led to the identification of a novel p53‐dependent biomarker of telomere dysfunction, S100A6.