AIB1 promotes DNA replication by JNK repression and AKT activation during cellular stress.
Amplified in breast cancer 1 (AIB1) is a member of the p160 family of nuclear receptor coactivator protein. Recent studies have reported that high-level AIB1 production is involved in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway for progression to malignant carcinoma in a steroid-independent manner. Here we demonstrate that, in AIB1-knockout DT40 chicken B-lymphocytes, loss of AIB1 results in induction of phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun, in addition to the inhibition of DNA replication. In contrast, high-level AIB1 production prevents proapoptotic activation of the JNK/c-Jun signal transduction pathway and induces DNA replication through phosphorylation of the Akt/p65 NF-kappaB subunit RelA under cellular stresses such as UV irradiation or serum deprivation. Moreover, we have found that AIB1 is essential for the phosphorylation of histone H3 at serine 10, which is associated with the signal transduction to chromatin, leading to the transient expression of immediate-early genes in response to UV stimulation. Our results therefore suggest that AIB1 directly links to cell cycle control mechanisms in concern with the balance between apoptosis and proliferation.
Horiguchi
Kikumi
K
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871.
Arai
Shigeki
S
Nishihara
Tsutomu
T
Nishikawa
Jun-ichi
J
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002645:Chickens; D017931:DNA Primers; D004261:DNA Replication; D004789:Enzyme Activation / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*
D017931:DNA Primers; D006657:Histones; D015534:Trans-Activators; D051548:Histone Acetyltransferases; D056921:Nuclear Receptor Coactivator 3; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases