| RRC ID |
35778
|
| 著者 |
Shrestha R, Tatsukawa H, Shrestha R, Ishibashi N, Matsuura T, Kagechika H, Kose S, Hitomi K, Imamoto N, Kojima S.
|
| タイトル |
Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
Nuclear accumulation of transglutaminase 2 (TG2) is an important step in TG2-dependent cell death. However, the underlying molecular mechanisms for nuclear translocation of TG2 are still poorly understood. In this study, we demonstrated that acyclic retinoid (ACR) induced nuclear accumulation of TG2 in JHH-7 cells, a hepatocellular carcinoma (HCC) leading to their apoptosis. We further demonstrated molecular mechanism in nuclear-cytoplasmic trafficking of TG2 and an effect of ACR on it. We identified a novel 14-amino acid nuclear localization signal (NLS) (466)AEKEETGMAMRIRV(479) in the 'C' domain and a leucine-rich nuclear export signal (NES) (657)LHMGLHKL(664) in the 'D' domain that allowed TG2 to shuttle between the nuclear and cytosolic milieu. Increased nuclear import of GAPDH myc-HIS fused with the identified NLS was observed, confirming its nuclear import ability. Leptomycin B, an inhibitor of exportin-1 as well as point mutation of all leucine residues to glutamine residues in the NES of TG2 demolished its nuclear export. TG2 formed a trimeric complex with importin-α and importin-β independently from transamidase activity which strongly suggested the involvement of a NLS-based translocation of TG2 to the nucleus. ACR accelerated the formation of the trimeric complex and that may be at least in part responsible for enhanced nuclear localization of TG2 in HCC cells treated with ACR.
|
| 巻・号 |
6(12)
|
| ページ |
e2002
|
| 公開日 |
2015-12-3
|
| DOI |
10.1038/cddis.2015.339
|
| PII |
cddis2015339
|
| PMID |
26633708
|
| PMC |
PMC4720877
|
| MeSH |
Amino Acid Sequence
Apoptosis / drug effects
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / enzymology*
Carcinoma, Hepatocellular / pathology
Cell Differentiation / drug effects
Cell Differentiation / physiology
Cell Line, Tumor
Cell Nucleus / drug effects
Cell Nucleus / enzymology
Cell Proliferation / drug effects
Cell Proliferation / physiology
GTP-Binding Proteins / metabolism*
Humans
Liver Neoplasms / drug therapy
Liver Neoplasms / enzymology*
Liver Neoplasms / pathology
Molecular Sequence Data
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases / metabolism*
Tretinoin / analogs & derivatives*
Tretinoin / pharmacology
|
| IF |
6.304
|
| 引用数 |
15
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
IRAL008I18 (HGY083410) |
