title: Parkin induces upregulation of 40S ribosomal protein SA and posttranslational modification of cytokeratins 8 and 18 in human cervical cancer cells.
abstract: Parkin was originally identified as a protein associated with Parkinson's disease. Recently, numerous research studies have suggested that parkin acts as a tumor suppressor. In accordance with these studies, we previously reported that overexpression of parkin in HeLa cells induced growth inhibition. To elucidate possible mechanisms by which parkin may inhibit cell growth, HeLa cells were infected with adenoviruses expressing either the parkin gene or adenovirus alone for 72 h and a total proteomic analysis was performed using 2-D gel electrophoresis followed by LC-MS/MS. We identified three proteins whose expression changed between the two groups: the 40S ribosomal protein SA (RPSA) was downregulated in parkin virus-infected cells, and cytokeratins 8 and 18 exhibited an acid shift in pI value without a change in molecular weight, suggesting that these proteins became phosphorylated in parkin virus-infected cells. The changes in these three proteins were first observed at 60 h postinfection and were most dramatic at 72 h postinfection. Because upregulation of RPSA and dephosphorylation of cytokeratins 8/18 have been linked with tumor progression, these data suggest that parkin may inhibit cell growth, at least in part, by decreasing RPSA expression and inducing phosphorylation of cytokeratin 8/18.
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology (KIST), Gangneung, 210-340, Republic of Korea.
authors.forename: Dae-Geun
authors.initials: DG
authors.lastname: Song
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jung
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.forename: Cheol-Ho
authors.initials: CH
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053538:Keratin-18 / Q000737:chemistry / Q000378:metabolism*; D053533:Keratin-8 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D017474:Receptors, Laminin / Q000737:chemistry / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D053538:Keratin-18; D053533:Keratin-8; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein