Disruption of RING and PHD Domains of TRIM28 Evokes Differentiation in Human iPSCs.
KAP1
TRIM28
cancer
differentiation
epigenetics
iPS
pluripotency
self-renewal
stem cells
stemness
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
29 07 2021
29 07 2021
Historique:
received:
20
06
2021
revised:
18
07
2021
accepted:
26
07
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
TRIM28, a multi-domain protein, is crucial in the development of mouse embryos and the maintenance of embryonic stem cells' (ESC) self-renewal potential. As the epigenetic factor modulating chromatin structure, TRIM28 regulates the expression of numerous genes and is associated with progression and poor prognosis in many types of cancer. Because of many similarities between highly dedifferentiated cancer cells and normal pluripotent stem cells, we applied human induced pluripotent stem cells (hiPSC) as a model for stemness studies. For the first time in hiPSC, we analyzed the function of individual TRIM28 domains. Here we demonstrate the essential role of a really interesting new gene (RING) domain and plant homeodomain (PHD) in regulating pluripotency maintenance and self-renewal capacity of hiPSC. Our data indicate that mutation within the RING or PHD domain leads to the loss of stem cell phenotypes and downregulation of the FGF signaling. Moreover, impairment of RING or PHD domain results in decreased proliferation and impedes embryoid body formation. In opposition to previous data indicating the impact of phosphorylation on TRIM28 function, our data suggest that TRIM28 phosphorylation does not significantly affect the pluripotency and self-renewal maintenance of hiPSC. Of note, iPSC with disrupted RING and PHD functions display downregulation of genes associated with tumor metastasis, which are considered important targets in cancer treatment. Our data suggest the potential use of RING and PHD domains of TRIM28 as targets in cancer therapy.
Identifiants
pubmed: 34440702
pii: cells10081933
doi: 10.3390/cells10081933
pmc: PMC8394524
pii:
doi:
Substances chimiques
TRIM28 protein, human
EC 2.3.2.27
Tripartite Motif-Containing Protein 28
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fundacja na rzecz Nauki Polskiej
ID : 2010-3/3
Organisme : Greater Poland Cancer Centre
ID : 17/2016/132
Organisme : Greater Poland Cancer Centre
ID : 22/2016/137
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