The cDNA cloning of the transcripts of human PEBP2αA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia

Zhang, Yuwen; Bae, Suk‐Chul; Takáhashi, Eiichi; Ito, Yoshiaki

doi:10.1038/sj.onc.1201352

Cited by 31 publications

(21 citation statements)

References 26 publications

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“…Protein levels of RUNX2 also increased with a concomitant increase in phosphorylated Akt (pAkt), which is a downstream component activated by IGF-1 and used here as a positive control for IGF-1 treatment. The presence of a lower molecular weight band of RUNX2 has been described before by our laboratory (13) and is the result of an alternative splicing event (13,49,50). The increase in RUNX2 activity was also time-dependent with up to 12-fold increase evident after 45 min in the presence of 20 ng/ml IGF-1 (Fig.…”

Section: Resultsmentioning

confidence: 63%

Insulin-like Growth Factor-1 Regulates Endogenous RUNX2 Activity in Endothelial Cells through a Phosphatidylinositol 3-Kinase/ERK-dependent and Akt-independent Signaling Pathway

Qiao

Shapiro

Kumar

et al. 2004

Journal of Biological Chemistry

135

102

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Section: Resultsmentioning

confidence: 63%

Insulin-like Growth Factor-1 Regulates Endogenous RUNX2 Activity in Endothelial Cells through a Phosphatidylinositol 3-Kinase/ERK-dependent and Akt-independent Signaling Pathway

Qiao

Shapiro

Kumar

et al. 2004

Journal of Biological Chemistry

135

102

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“…In addition, the corresponding heterozygous mice displayed a phenotype that resembled that of human cleidocranial dysplasia syndrome, which has been linked to defect(s) in one allele of the PEBP2␣A/ CBFA1 gene (40,62). These analyses in mice and humans present strong evidence in favor of PEBP2 involvement in multiple aspects of mammalian embryogenesis and suggest that PEBP2 acts in a specific way at each gene.…”

mentioning

confidence: 72%

Intrinsic Transcriptional Activation-Inhibition Domains of the Polyomavirus Enhancer Binding Protein 2/Core Binding Factor α Subunit Revealed in the Presence of the β Subunit

Kanno

Chen

et al. 1998

Molecular and Cellular Biology

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185

212

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A member of the polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is composed of PEBP2␣B1/AML1 (as the ␣ subunit) and a ␤ subunit. It plays an essential role in definitive hematopoiesis and is frequently involved in the chromosomal abnormalities associated with leukemia. In the present study, we report functionally separable modular structures in PEBP2␣B1 for DNA binding and for transcriptional activation. DNA binding through the Runt domain of PEBP2␣B1 was hindered by the adjacent carboxyterminal region, and this inhibition was relieved by interaction with the ␤ subunit. Utilizing a reporter assay system in which both the ␣ and ␤ subunits are required to achieve strong transactivation, we uncovered the presence of transcriptional activation and inhibitory domains in PEBP2␣B1 that were only apparent in the presence of the ␤ subunit. The inhibitory domain keeps the full transactivation potential of full-length PEBP2␣B1 below its maximum potential. Fusion of the transactivation domain of PEBP2␣B1 to the yeast GAL4 DNA-binding domain conferred transactivation potential, but further addition of the inhibitory domain diminished the activity. These results suggest that the activity of the ␣ subunit as a transcriptional activator is regulated intramolecularly as well as by the ␤ subunit. PEBP2␣B1 and the ␤ subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal. Moreover, the transactivation domain by itself was capable of associating with the nuclear matrix, which implies the existence of a relationship between transactivation and nuclear matrix attachment.The polyomavirus enhancer binding protein 2 (PEBP2), also called core binding factor (CBF), is a transcription factor complex composed of ␣ and ␤ subunits (reviewed in references 21 and 51). The ␣ subunit binds to DNA and harbors the transactivating activity, while the ␤ subunit enhances the DNA binding activity of the ␣ subunit. In mammals, members of the ␣ subunit family are encoded by three genes, PEBP2␣A/ CBFA1/AML3, PEBP2␣B/CBFA2/AML1, and PEBP2␣C/ CBFA3/AML2, and all belong to the Runt domain gene family, which includes the Drosophila genes runt and lozenge. The ␤ subunit is encoded by a single gene, PEBP2␤/CBFB, whereas two genes, brother and big brother have been identified in Drosophila.Among the three mammalian ␣ subunit genes, PEBP2␣B/ CBFA2/AML1 (2, 36, 51) is disrupted in chromosomal translocations associated with several types of leukemia, including the M2 subtype of the French-American-British classification of leukemia, which is characterized by the 8-to-21 chromosome translocation [t(8;21)], and childhood acute lymphoblastic leukemia with the associated t(12;21) translocation. The t(8;21) and t(12;21) translocations produce the chimeric proteins, AML1/ETO(MTG8) and TEL-AML1, respectively (13,19,37). These proteins retain the entire Runt domain in their PEBP2␣B/AML1 portions, which is essential and sufficient for dimerization with the ␤ subunit and for DNA binding. In addition, it is...

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“…We and our colleagues have mapped the ␣A/CBFA1 gene to chromosome 6p21 (Levanon et al 1994;Lee et al 1997;Zhang et al 1997), which is also the genetic locus for an autosomal dominant human bone disease, cleidocranial dysplasia (CCD) syndrome (Mundlos et al 1995). CCD is characterized by hypoplastic or aplastic clavicles, patent fontanelles and sutures, and other bone malformations (Jones 1997).…”

Section: ␣A/cbfa1mentioning

confidence: 99%

Molecular basis of tissue‐specific gene expression mediated by the Runt domain transcription factor PEBP2/CBF

1999

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The Runt domain transcription factor PEBP2/CBF is a heterodimer of ␣ and ␤ subunits. Of the three mammalian ␣ subunit genes, which are homologues of the Drosophila gene runt, PEBP2␣A/CBFA1 and PEBP2␣B/AML1 are critical regulators of osteogenesis and haematopoiesis, respectively. A unique functional interaction between PEBP2␣B/AML1 and Ets-1 was recently observed, and provides a clear example of context-dependent transcriptional regulation. An elaborate mechanism of cooperation between the two factors may represent a basis for tissuespecific gene expression, which is thought to be achieved by combinations of specific sets of transcription factors unique to each cell lineage or stage of differentiation. A possible molecular basis for the critical role(s) played by PEBP2/CBF in tissue determination is discussed in light of these observations.

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The cDNA cloning of the transcripts of human PEBP2αA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia

Cited by 31 publications

References 26 publications

Insulin-like Growth Factor-1 Regulates Endogenous RUNX2 Activity in Endothelial Cells through a Phosphatidylinositol 3-Kinase/ERK-dependent and Akt-independent Signaling Pathway

Insulin-like Growth Factor-1 Regulates Endogenous RUNX2 Activity in Endothelial Cells through a Phosphatidylinositol 3-Kinase/ERK-dependent and Akt-independent Signaling Pathway

Intrinsic Transcriptional Activation-Inhibition Domains of the Polyomavirus Enhancer Binding Protein 2/Core Binding Factor α Subunit Revealed in the Presence of the β Subunit

Molecular basis of tissue‐specific gene expression mediated by the Runt domain transcription factor PEBP2/CBF

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