TY - JOUR
T1 - Epigenetic alterations of BRG1 leads to cancer development through its nuclear-cytoplasmic shuttling abnormalities
AU - Gunduz, Esra
AU - Gunduz, Mehmet
AU - Nagatsuka, Hitoshi
AU - Beder, Levent
AU - Demircan, Kadir
AU - Tamamura, Ryo
AU - Hatipoglu, Omer Faruk
AU - Mahmut, Naila
AU - Katase, Naoki
AU - Naomoto, Yoshio
AU - Nagai, Noriyuki
N1 - Funding Information:
This work was partially supported by grants-in-aid for scientific researches from the Ministry of Education, Culture, Sports, Science and Technology (#17591911, 17591910, 15209060, and 17406027).
PY - 2006
Y1 - 2006
N2 - SWI/SNF is a multiprotein chromatin remodeling complex important for gene regulation. BRG1 and its close relative BRM, have ATPase activity necessary for transcriptional regulation by conformational change of nucleosomes. Due to this role on gene expression, several members of SWI/SNF complex including BRG1 and BRM function as a tumor suppressor or negative regulator of cellular proliferation. On the other hand, the shuttling of proteins between nucleus and cytoplasm is strongly involved in the regulation of cell cycle and proliferation. Many of tumor suppressor gene (TSG)s including p53, BRCA1, ING1 play some of their functions through nucleocytoplasmic shuttling. Abnormalities related with this process abrogate the subcellular localization of the TSGs and lead to cancer development. We recently demonstrated BRG1 as a TSG in oral cancer. Our analysis also revealed an interesting finding that one of the splicing forms of BRG1 is selectively lost in cancer tissue as compared to normal counterparts. Our further analysis revealed a putative nuclear retention signal domain for this splicing form. In this article, we speculate the possible mechanism for the inactivation of BRG1 gene in oral cancer through an abnormality in its subcellular localization.
AB - SWI/SNF is a multiprotein chromatin remodeling complex important for gene regulation. BRG1 and its close relative BRM, have ATPase activity necessary for transcriptional regulation by conformational change of nucleosomes. Due to this role on gene expression, several members of SWI/SNF complex including BRG1 and BRM function as a tumor suppressor or negative regulator of cellular proliferation. On the other hand, the shuttling of proteins between nucleus and cytoplasm is strongly involved in the regulation of cell cycle and proliferation. Many of tumor suppressor gene (TSG)s including p53, BRCA1, ING1 play some of their functions through nucleocytoplasmic shuttling. Abnormalities related with this process abrogate the subcellular localization of the TSGs and lead to cancer development. We recently demonstrated BRG1 as a TSG in oral cancer. Our analysis also revealed an interesting finding that one of the splicing forms of BRG1 is selectively lost in cancer tissue as compared to normal counterparts. Our further analysis revealed a putative nuclear retention signal domain for this splicing form. In this article, we speculate the possible mechanism for the inactivation of BRG1 gene in oral cancer through an abnormality in its subcellular localization.
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U2 - 10.1016/j.mehy.2006.05.032
DO - 10.1016/j.mehy.2006.05.032
M3 - Article
C2 - 16824695
AN - SCOPUS:33748953340
VL - 67
SP - 1313
EP - 1316
JO - Medical Hypotheses
JF - Medical Hypotheses
SN - 0306-9877
IS - 6
ER -
