title: Hsp22 (HspB8/H11) knockdown induces Sam68 expression and stimulates proliferation of glioblastoma cells.
abstract: Sam68 (Src-associated protein in mitosis 68 kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein, altered cellular morphology, and enhanced cell proliferation. This heightened proliferation was associated with a sharp decrease in G(0) /G(1) and a corresponding increase in S and G(2) /M phases in exponentially growing cultures. The increased S phase population in turn correlated with enhanced expression of cell cycle regulatory proteins such as cyclin E, cyclin A, ribonucleotide reductase (RNR), and proliferating cell nuclear antigen (PCNA), which are required for the transition of cells from G(1) to S phase. Collectively, our results demonstrate for the first time that Hsp22 regulates Sam68 expression and the ratio of Sam68 to Hsp22 may determine the proliferative potential of glioblastoma cells.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Suhasini
authors.initials: S
authors.lastname: Modem
authors.forename: Kannagi
authors.initials: K
authors.lastname: Chinnakannu
authors.forename: Uma
authors.initials: U
authors.lastname: Bai
authors.forename: G Prem-Veer
authors.initials: GP
authors.lastname: Reddy
authors.forename: Thipparthi R
authors.initials: TR
authors.lastname: Reddy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; C489559:KHDRBS1 protein, human; D018832:Molecular Chaperones; D016601:RNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases