[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Oct 2006 · Journal of Biochemistry
[Show abstract][Hide abstract] ABSTRACT: The factors SRC-1, TIF2 and ACTR were identified as interacting with nuclear receptors in a highly ligand-dependent manner. Because the molecular mass of each of these factors is approximately 160 kDa, they are collectively termed p160 coactivators. So far, p160 coactivators have been cloned from human, mouse and Xenopus. We report here the cloning of the chicken homologues of p160 coactivator members. As in human and mouse, chicken has three p160 coactivators. Each gene encodes an approximately 160 kDa protein which exhibits 70-80% amino acid sequence identity to human and mouse p160 coactivators. Chicken p160 coactivators also have the property of interacting with several liganded nuclear receptors. Moreover, we describe an imperfect LXXLL sequence, termed NR box 4, which is located downstream of NR box 3 and conserved between evolutionarily diverse species. The loss of NR box 4 results in a decrease of interaction with the nuclear receptor, which indicates that NR box 4 is required for efficient interaction.
No preview · Article · Apr 2001 · Biochimica et Biophysica Acta
[Show abstract][Hide abstract] ABSTRACT: Iα25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active form of vitamin D3, has been thought to be a multifunctional agent. In order to discover novel roles of 1,26-(OH)2D3, we have been looking for new genes that are regulated by 1,25-(OH)2D3. Because the actions of 1,25-(OH)2D3 are mediated through the vitamin D receptor (VDR), that is a DNA binding transcription factor, vitamin D regulated genes
should have VDR binding sites in their regulatory regions. In this paper, we describe a novel vitamin D response element (VDRE)-
containing sequence, clone 3, which was isolated through binding to VDR. DNA sequence analysis of clone 3 did not reveal any
significant similarity with sequences reported previously. Clone 3 had two regions consisting of a direct repeated sequence
of AGTTCA motifs, both of which bound to VDR independently. Whereas each direct repeat sequence alone could not mediate transcriptional
activation efficiently, with their co-existence there was a strong response to 1,25-(OH)2D3, indicating that these two direct repeated sequences act cooperatively.
No preview · Article · Feb 1997 · Journal of Biochemistry
[Show abstract][Hide abstract] ABSTRACT: The vitamin D receptor (VDR) binds to the vitamin D response element (VDRE) in the promoter region of target genes and acts as a ligand-dependent transcriptional regulator. In order to identify novel VDREs and new genes that are regulated by the active form of vitamin D [1,25-(OH)2D3], rat genomic DNA fragments bound by VDR were isolated. One of these fragments, designated as VBF5 was transcribed and the transcript was down-regulated by 1,25-(OH)2D3. These data strongly indicate that VBF5 may contain a VDRE regulating negatively an unidentified gene expression.
No preview · Article · Mar 1996 · Biochemical and Biophysical Research Communications