지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 134 - 144 (11page)
이용수
초록· 키워드
오류제보하기
Purpose The RAS association domain family protein 1 (RASSF1) has been implicated in a tumor-suppressive function through the induction of acetylated α-tubulin and modulation of cell migration. However, the mechanisms of how RASSF1A is associated with acetylation of α-tubulin for controlling cell migration have not yet been elucidated. In this study, we found that RASSF1A regulated cell migration through the regulation of histon deacetylase 6 (HDAC6), which functions as a tubulin deacetylase.
Materials and Methods The cell migration was assessed using wound-healing and transwell assays. The role of RASSF1A on cell migration was examined by immunofluorescence staining, HDAC activity assay and western blot analysis.
Results Cell migration was inhibited and cell morphology was changed in RASSF1A-transfected H1299 cells, compared with controls, whereas HDAC6 protein expression was not changed by RASSF1A transfection in these cells. However, RASSF1A inhibited deacetylating activity of HDAC6 protein and induced acetylated α-tubulin expression.
Furthermore, acetylated α-tubulin and HDAC6 protein were co-localized in the cytoplasm in RASSF1A-transfected H1299 cells. Conversely, when the endogenous RASSF1A expression in HeLa cells was blocked with RASSF1A siRNA treatment, acetylated α-tubulin was co-localized with HDAC6 protein throughout the whole cells,including the nucleus, compared with scramble siRNA-treated HeLa cells. The restoration of RASSF1A by 5-Aza-dC treatment also induced acetylated α-tubulin through inhibition of HDAC6 activity that finally resulted in suppressing cell migration in H1299cells. To further confirm the role of HDAC6 in RASSF1A-mediated cell migration, the HDAC6 expression in H1299 cells was suppressed by using HDAC6 siRNA, and cell motility was found to be decreased through enhanced acetylated α-tubulin.
Conclusion The results of this study suggest that the inactivation of HDAC6 by RASSF1A regulates cell migration through increased acetylated α-tubulin protein.
목차
등록된 정보가 없습니다.
참고문헌 (25)
참고문헌 신청
Agathanggelou A / 2003 / Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cance
Agathanggelou A / 2005 / Role of the Ras-association domain family 1 tumor suppressor gene in human cancers / Cancer Res 65 : 3497 ~ 3508
Ahmed-Choudhury J / 2005 / Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter / Cancer Res 65 : 2690 ~ 2697
Aoyama Y / 2004 / Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases / Oncogene 23 : 3426 ~ 3433
Avruch J / 2006 / Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases / Methods Enzymol 407 : 290 ~ 310
Agathanggelou A / 2005 / Role of the Ras-association domain family 1 tumor suppressor gene in human cancers / Cancer Res 65 : 3497 ~ 3508
Ahmed-Choudhury J / 2005 / Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter / Cancer Res 65 : 2690 ~ 2697
Aoyama Y / 2004 / Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases / Oncogene 23 : 3426 ~ 3433
Avruch J / 2006 / Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases / Methods Enzymol 407 : 290 ~ 310
이 논문의 저자 정보
최근 본 자료
댓글(0)
0