TY - JOUR
T1 - Hbo1 links p53-dependent stress signaling to DNA replication licensing
AU - Iizuka, Masayoshi
AU - Sarmento, Olga F.
AU - Sekiya, Takao
AU - Scrable, Heidi
AU - Allis, C. David
AU - Smith, M. Mitchell
PY - 2008/1
Y1 - 2008/1
N2 - Hbo1 is a histone acetyltransferase (HAT) that is required for global histone H4 acetylation, steroid-dependent transcription, and chromatin loading of MCM2-7 during DNA replication licensing. It is the catalytic subunit of protein complexes that include ING and JADE proteins, growth regulatory factors and candidate tumor suppressors. These complexes are thought to act via tumor suppressor p53, but the molecular mechanisms and links between stress signaling and chromatin, are currently unknown. Here, we show that p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Two physiological stresses that stabilize p53, hyperosmotic shock and DNA replication fork arrest, also inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 phase specifically inhibits the loading of the MCM2-7 complex, providing an example of the chromatin output of this pathway. These results reveal a direct regulatory connection between p53-responsive stress signaling and Hbo1-dependent chromatin pathways.
AB - Hbo1 is a histone acetyltransferase (HAT) that is required for global histone H4 acetylation, steroid-dependent transcription, and chromatin loading of MCM2-7 during DNA replication licensing. It is the catalytic subunit of protein complexes that include ING and JADE proteins, growth regulatory factors and candidate tumor suppressors. These complexes are thought to act via tumor suppressor p53, but the molecular mechanisms and links between stress signaling and chromatin, are currently unknown. Here, we show that p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Two physiological stresses that stabilize p53, hyperosmotic shock and DNA replication fork arrest, also inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 phase specifically inhibits the loading of the MCM2-7 complex, providing an example of the chromatin output of this pathway. These results reveal a direct regulatory connection between p53-responsive stress signaling and Hbo1-dependent chromatin pathways.
UR - http://www.scopus.com/inward/record.url?scp=37549064391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37549064391&partnerID=8YFLogxK
U2 - 10.1128/MCB.00662-07
DO - 10.1128/MCB.00662-07
M3 - Article
C2 - 17954561
AN - SCOPUS:37549064391
SN - 0270-7306
VL - 28
SP - 140
EP - 153
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 1
ER -