| RRC ID |
85096
|
| Author |
Tsunematsu T, Mouri Y, Shao W, Arakaki R, Ruppert JG, Murano K, Ishimaru N, Guardavaccaro D, Pagano M, Kudo Y.
|
| Title |
Sustained chromosomal passenger complex activity preserves the pluripotency of human embryonic carcinoma cells.
|
| Journal |
Sci Signal
|
| Abstract |
Human embryonic carcinoma (hEC) cells are derived from teratocarcinomas, exhibit robust proliferation, have a high differentiation potential, are the malignant counterparts of human embryonic stem cells (hESCs), and are considered hESC-like. The chromosomal passenger complex (CPC), made up of the microtuble binding protein Borealin, the kinase Aurora-B, the CPC-stabilizing inner centromere protein (INCENP), and the inhibitor of apoptosis family member Survivin, regulates cell division and is active exclusively during mitosis in somatic cells. The anaphase-promoting complex/cyclosome and its cofactor Cdh1 (APC/CCdh1) is a ubiquitylating complex that catalyzes the degradation of Aurora-B and Borealin in somatic cells but has low activity during interphase in hESCs. Here, we found that Borealin and Aurora-B exhibited sustained stability throughout the cell cycle of hEC cells due to low APC/CCdh1 activity. In contrast with somatic cells, CPC activity persisted across the cell cycle of hEC cells because of diminished APC/CCdh1 activity. Disrupting the CPC complex by depleting its constituents triggered spontaneous differentiation in hEC cells. As hEC cells differentiated, APC/CCdh1 activation curtailed CPC activity. Inactivating the CPC by pharmacologically inhibiting Aurora-B induced hEC cell differentiation by activating the epithelial-to-mesenchymal transition (EMT) program. Hence, APC/CCdh1-mediated termination of CPC activity triggered hEC cell differentiation. Collectively, these findings demonstrate a role for the CPC in governing hESC cell fate.
|
| Volume |
18(874)
|
| Pages |
eadg4626
|
| Published |
2025-2-18
|
| DOI |
10.1126/scisignal.adg4626
|
| PMID |
40136047
|
| MeSH |
Anaphase-Promoting Complex-Cyclosome / metabolism
Antigens, CD
Aurora Kinase B* / genetics
Aurora Kinase B* / metabolism
Cadherins / genetics
Cadherins / metabolism
Cell Cycle Proteins* / genetics
Cell Cycle Proteins* / metabolism
Cell Differentiation
Cell Line, Tumor
Chromosomal Proteins, Non-Histone* / genetics
Chromosomal Proteins, Non-Histone* / metabolism
Humans
Pluripotent Stem Cells* / metabolism
Survivin
|
| IF |
6.467
|
| Resource |
| DNA material |
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
| Human and Animal Cells |
201B7(HPS0063) |
