Unknown

Dataset Information

0

Fos-dependent induction of Chk1 protects osteoblasts from replication stress.


ABSTRACT: Stable Fos expression in the osteoblast lineage results in the development of osteosarcomas (OS) in mice, yet the underlying mechanisms are poorly understood. Using a genetic system in which Fos expression can be induced in osteoblasts in a doxycycline-dependent manner and through subsequent RNA sequencing and gene set enrichment analysis, we were able to identify novel transcriptional targets of Fos in osteoblasts. These included a distinct activation of cellular response toward replication stress (RS), exemplified by a Fos-dependent induction of the RS-suppressing Chk1 kinase. Importantly, Fos expression protects osteoblasts from RS and DNA damage likely through upregulation of Chk1 and facilitates transformation by Ras/E1A oncogenes. These data reveal a novel function of Fos in safeguarding genome stability during replication, which is particularly relevant in conditions of oncogene-induced S-phase entry.

SUBMITTER: Schulze J 

PROVIDER: S-EPMC4111761 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Fos-dependent induction of Chk1 protects osteoblasts from replication stress.

Schulze Jochen J   Lopez-Contreras Andres J AJ   Uluçkan Özge Ö   Graña-Castro Osvaldo O   Fernandez-Capetillo Oscar O   Wagner Erwin F EF  

Cell cycle (Georgetown, Tex.) 20140424 12


Stable Fos expression in the osteoblast lineage results in the development of osteosarcomas (OS) in mice, yet the underlying mechanisms are poorly understood. Using a genetic system in which Fos expression can be induced in osteoblasts in a doxycycline-dependent manner and through subsequent RNA sequencing and gene set enrichment analysis, we were able to identify novel transcriptional targets of Fos in osteoblasts. These included a distinct activation of cellular response toward replication str  ...[more]

Similar Datasets

| S-EPMC5879462 | biostudies-literature
| S-EPMC2607051 | biostudies-literature
| S-EPMC5816205 | biostudies-literature
| S-EPMC7761918 | biostudies-literature
| S-EPMC4691220 | biostudies-literature
2021-01-01 | GSE158338 | GEO
| S-EPMC1345677 | biostudies-literature
| S-EPMC5357902 | biostudies-literature
| S-EPMC7308455 | biostudies-literature
| S-EPMC3730229 | biostudies-literature