title: Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.
abstract: 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.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Ku
authors.forename: Dae-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Gong
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: autophagy; kidney cancer; protein cross-linking