Publications

Authors:

Tsunematsu, Takaaki; Mouri, Yasuhiro; Shao, Wenhua; Arakaki, Rieko; Ruppert, Jan G.; Murano, Kensaku; Ishimaru, Naozumi; Guardavaccaro, Daniele; Pagano, Michele; Kudo, Yasusei

Title:

Sustained chromosomal passenger complex activity preserves the pluripotency of human embryonic carcinoma cells

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

SCIENCE SIGNALING

ISSN of journal:

1937-9145

N° Volume:

18

Number or Folder:

874

Page numbers:

1-16

Keyword:

Human embryonic carcinoma, pluripotency, APC/CCdh1

Short description of contents:

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.

Product ID:

144543

Handle IRIS:

11562/1156747

Last Modified:

March 8, 2025

Bibliographic citation:

Tsunematsu, Takaaki; Mouri, Yasuhiro; Shao, Wenhua; Arakaki, Rieko; Ruppert, Jan G.; Murano, Kensaku; Ishimaru, Naozumi; Guardavaccaro, Daniele; Pagano, Michele; Kudo, Yasusei, Sustained chromosomal passenger complex activity preserves the pluripotency of human embryonic carcinoma cells «SCIENCE SIGNALING» , vol. 18 , n. 874 , 2025 , pp. 1-16

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