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Hsp22 (HspB8/H11) knockdown induces sam68 expression and stimulates proliferation of glioblastoma cells
Author(s) -
Modem Suhasini,
Chinnakannu Kannagi,
Bai Uma,
Reddy G. PremVeer,
Reddy Thipparthi R.
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22868
Subject(s) - gene knockdown , cell growth , biology , cell cycle , jurkat cells , microbiology and biotechnology , mitosis , cell culture , cell , t cell , biochemistry , immunology , immune system , genetics
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. J. Cell. Physiol. 226: 2747–2751, 2011. © 2011 Wiley‐Liss, Inc.