Fos-dependent induction of Chk1 protects osteoblasts from replication stress

Jochen Schulze; Andres J Lopez-Contreras; Özge Uluçkan; Osvaldo Graña-Castro; Oscar Fernandez-Capetillo; Erwin F Wagner

doi:10.4161/cc.28923

Fos-dependent induction of Chk1 protects osteoblasts from replication stress

Jochen Schulze, Andres J Lopez-Contreras, Özge Uluçkan, Osvaldo Graña-Castro, Oscar Fernandez-Capetillo, Erwin F Wagner

11 Citationer (Scopus)

Abstract

Stable Fos expression in the osteoblast lineage results in the development of steosarcomas (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.

Originalsprog	Engelsk
Tidsskrift	Cell Cycle
Vol/bind	13
Udgave nummer	12
Sider (fra-til)	1980-6
Antal sider	7
ISSN	1538-4101
DOI	https://doi.org/10.4161/cc.28923
Status	Udgivet - 15 jun. 2014
Udgivet eksternt	Ja

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10.4161/cc.28923

Citationsformater

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title = "Fos-dependent induction of Chk1 protects osteoblasts from replication stress",

abstract = "Stable Fos expression in the osteoblast lineage results in the development of steosarcomas (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.",

keywords = "Animals, Cells, Cultured, DNA Damage, DNA Replication, Gene Knockout Techniques, Mice, Oncogene Proteins v-fos, Osteoblasts, Protein Kinases, Tumor Suppressor Protein p53",

author = "Jochen Schulze and Lopez-Contreras, {Andres J} and {\"O}zge Ulu{\c c}kan and Osvaldo Gra{\~n}a-Castro and Oscar Fernandez-Capetillo and Wagner, {Erwin F}",

year = "2014",

month = jun,

day = "15",

doi = "10.4161/cc.28923",

language = "English",

volume = "13",

pages = "1980--6",

journal = "Cell Cycle",

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TY - JOUR

T1 - Fos-dependent induction of Chk1 protects osteoblasts from replication stress

AU - Schulze, Jochen

AU - Lopez-Contreras, Andres J

AU - Uluçkan, Özge

AU - Graña-Castro, Osvaldo

AU - Fernandez-Capetillo, Oscar

AU - Wagner, Erwin F

PY - 2014/6/15

Y1 - 2014/6/15

N2 - Stable Fos expression in the osteoblast lineage results in the development of steosarcomas (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.

AB - Stable Fos expression in the osteoblast lineage results in the development of steosarcomas (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.

KW - Animals

KW - Cells, Cultured

KW - DNA Damage

KW - DNA Replication

KW - Gene Knockout Techniques

KW - Mice

KW - Oncogene Proteins v-fos

KW - Osteoblasts

KW - Protein Kinases

KW - Tumor Suppressor Protein p53

U2 - 10.4161/cc.28923

DO - 10.4161/cc.28923

M3 - Journal article

C2 - 24762558

SN - 1538-4101

VL - 13

SP - 1980

EP - 1986

JO - Cell Cycle

JF - Cell Cycle

IS - 12

ER -

Fos-dependent induction of Chk1 protects osteoblasts from replication stress

Abstract

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