Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma
  • Ku, Bo Mi
  • Kim, Dae-Seok
  • Kim, Kyung-Hee
  • Yoo, Byong Chul
  • Kim, Seok-Hyun
  • 외 2명
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초록

Renal cell carcinoma (RCC), the predominant form of kidney cancer, is characterized by high resistance to radiation and chemotherapy. This study shows that expression of protein cross-linking enzyme transglutaminase 2 (TGase 2) is markedly increased in 7 renal cell carcinoma (RCC) cell lines in comparison to HEK293 and other cancer cell lines, such as NCI 60. However, the key role of TGase 2 in RCC was not clear. The down-regulation of TGase 2 was found to stabilize p53 expression, thereby inducing a 3- to 10-fold increase in apoptosis for 786-O, A498, CAKI-1, and ACHN cell lines by DAPI staining. MEF cells from TGase 2(-/-) mice showed stabilized p53 under apoptotic stress to compare to MEFs from wild-type mice. TGase 2 directly cross links the DNA binding domain of p53, leading to p53 depletion via autophagy in RCC. TGase 2 and p53 expression showed an inverse relationship in RCC cells. This finding implies that induced expression of TGase 2 promotes tumor cell survival through p53 depletion in RCC.Ku, B.M., Kim, D.-S. Kim, K.-H., Yoo, B.C., Kim, S.-H., Gong, Y.-D., Kim, S.-Y. Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.

키워드

kidney cancerautophagyprotein cross-linkingCROSS-LINKING ENZYMESTISSUE TRANSGLUTAMINASECANCER-CELLSSURVIVALDISEASEPROTEINPATHWAYCOMPLEXALPHA
제목
Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma
저자
Ku, Bo MiKim, Dae-SeokKim, Kyung-HeeYoo, Byong ChulKim, Seok-HyunGong, Young-DaeKim, Soo-Youl
DOI
10.1096/fj.12-224220
발행일
2013-09
유형
Article
저널명
FASEB Journal
27
9
페이지
3487 ~ 3495