<i>Prep2</i>: Cloning and expression of a new prep family member

Haller, Klaus; Rambaldi, Isabel; Kovács, Erzsébet Nagy; Daniels, Eugene; Featherstone, Mark

doi:10.1002/dvdy.10167

Cited by 29 publications

(40 citation statements)

References 43 publications

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“…Both PREP1 and PREP2 have been shown to accumulate in the cytoplasm of cultured and embryonic cells (19,28,29). When we used an affinitypurified antibody directed against an N-terminal epitope to assess PREP2 distribution in the mouse embryo, we noted widespread but essentially cytoplasmic expression (29). We report here that a second affinity-purified antibody directed against the PREP2 C terminus reveals nuclear staining and that between them the two antibodies recognize at least five distinct PREP2 isoforms.…”

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confidence: 74%

“…In complexes with PBX, PREP1 regulates the transcription of HOX-dependent (Hoxb2) and HOX-independent (urokinase plasminogen activator, glucagon) target genes (5,9,10). Both PREP1 and PREP2 have been shown to accumulate in the cytoplasm of cultured and embryonic cells (19,28,29). When we used an affinitypurified antibody directed against an N-terminal epitope to assess PREP2 distribution in the mouse embryo, we noted widespread but essentially cytoplasmic expression (29).…”

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confidence: 96%

“…MEIS binding masks NES while exposing NLS within the PBC N terminus (18 -20). Reciprocally, MEIS is dependent on PBX for nuclear localization (21-24).Recently, it has been shown in fly embryos and mammalian cells that PBX is retained in the cytoplasm by interaction with nonmuscle myosin heavy chain II B (22), raising the possibility that subcellular localization of TALE class proteins could be influenced by signaling pathways impinging on the cytoskeleton.The PREP (also known as PKNOX) (25) family has two members in mice and humans (9,(25)(26)(27)(28)(29). In complexes with PBX, PREP1 regulates the transcription of HOX-dependent (Hoxb2) and HOX-independent (urokinase plasminogen activator, glucagon) target genes (5, 9, 10).…”

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confidence: 99%

“…The PREP (also known as PKNOX) (25) family has two members in mice and humans (9,(25)(26)(27)(28)(29). In complexes with PBX, PREP1 regulates the transcription of HOX-dependent (Hoxb2) and HOX-independent (urokinase plasminogen activator, glucagon) target genes (5, 9, 10).…”

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confidence: 99%

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Subcellular Localization of Multiple PREP2 Isoforms Is Regulated by Actin, Tubulin, and Nuclear Export

Haller

Rambaldi²,

Daniels

et al. 2004

Journal of Biological Chemistry

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The PREP, MEIS, and PBX families are mammalian members of the TALE (three amino acid loop extension) class of homeodomain-containing transcription factors. These factors have been implicated in cooperative DNA binding with the HOX class of homeoproteins, but PREP and MEIS interact with PBX in apparently non-HOX-dependent cooperative DNA binding as well. PREP, MEIS, and PBX have all been reported to reside in the cytoplasm in one or more tissues of the developing vertebrate embryo. In the case of PBX, cytoplasmic localization is due to the modulation of nuclear localization signals, nuclear export sequences, and interaction with a cytoplasmic anchoring factor, non-muscle myosin heavy chain II B. Here we report that murine PREP2 exists in multiple isoforms distinguished by interaction with affinity-purified antibodies raised to N-and C-terminal epitopes and by nuclear versus cytoplasmic localization. Alternative splicing gives rise to some of these PREP2 isoforms, including a 25-kDa variant lacking the C-terminal half of the protein and homeodomain and having the potential to act as dominant-negative. We further show that cytoplasmic localization is due to the concerted action of nuclear export, as evidenced by sensitivity to leptomycin B, and cytoplasmic retention by the actin and microtubule cytoskeletons. Cytoplasmic PREP2 colocalizes with both the actin and microtubule cytoskeletons and coimmunoprecipitates with actin and tubulin. Importantly, disruption of either cytoskeletal system redirects cytoplasmic PREP2 to the nucleus. We suggest that transcriptional regulation by PREP2 is modulated through the subcellular distribution of multiple isoforms and by interaction with two distinct cytoskeletal systems.Patterning of the embryonic antero-posterior axis comes under the control of HOX and TALE 1 class homeoproteins (1).Members of the TALE class are characterized by sequence relatedness and by a three amino acid loop extension between helices one and two of the homeodomain (2). Families within the TALE group include PBC, MEIS, and PREP. Among the PBC family members, the fly extradenticle and vertebrate PBX proteins have been most intensively studied. PBC proteins bind DNA cooperatively with many but not all HOX proteins. Additionally, they form stable DNA-binding heterodimers with MEIS and PREP family members (2). The ability of PBC proteins to interact with both HOX and MEIS/PREP partners results in DNA-bound heterotrimeric complexes that have been implicated in gene control in vitro and in vivo (3-8). However, the instances of HOX-independent gene control by TALE heterodimers have also been documented (9, 10), consistent with the presence of these proteins in tissues devoid of Hox gene expression. In addition to the homeodomain, two conserved N-terminal domains, PBC-A and PBC-B, have been defined in PBC family proteins (11). These regions are implicated in numerous processes including nuclear export, transcriptional repression, MEIS/PREP interaction, and binding to non-muscle myosin heavy chain II B (2). Verte...

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confidence: 74%

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confidence: 96%

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confidence: 99%

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Subcellular Localization of Multiple PREP2 Isoforms Is Regulated by Actin, Tubulin, and Nuclear Export

Haller

Rambaldi²,

Daniels

et al. 2004

Journal of Biological Chemistry

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“…PKNOX2/PREP2, encoding a transcription factor, is located at the 11q24.2 breakpoint. [28][29][30] The reference sequence (NM_022062) for this gene is probably incomplete; further 5 0 exons extending to a CpG island are present in several ESTs (e.g. BC045626).…”

Section: Characterization Of Loci Affected By the Karyotype Rearrangementioning

confidence: 99%

Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder

et al. 2006

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In the search for the biological causes of schizophrenia and bipolar disorder, glutamate neurotransmission has emerged as one of a number of candidate processes and pathways where underlying gene deficits may be present. The analysis of chromosomal rearrangements in individuals diagnosed with neuropsychiatric disorders is an established route to candidate gene identification in both Mendelian and complex disorders. Here we describe a set of genes disrupted by, or proximal to, chromosomal breakpoints (2p12, 2q31.3, 2q21.2, 11q23.3 and 11q24.2) in a patient where chronic schizophrenia coexists with mild learning disability (US: mental retardation). Of these disrupted genes, the most promising candidate is a member of the kainate-type ionotropic glutamate receptor family, GRIK4 (KA1). A subsequent systematic case-control association study on GRIK4 assessed its contribution to psychiatric illness in the karyotypically normal population. This identified two discrete regions of disease risk within the GRIK4 locus: three single single nucleotide polymorphism (SNP) markers with a corresponding underlying haplotype associated with susceptibility to schizophrenia (P = 0.0005, odds ratio (OR) of 1.453, 95% CI 1.182-1.787) and two single SNP markers and a haplotype associated with a protective effect against bipolar disorder (P = 0.0002, OR of 0.624, 95% CI 0.485-0.802). After permutation analysis to correct for multiple testing, schizophrenia and bipolar disorder haplotypes remained significant (P = 0.0430, s.e. 0.0064 and P = 0.0190, s.e. 0.0043, respectively). We propose that these convergent cytogenetic and genetic findings provide molecular evidence for common aetiologies for different psychiatric conditions and further support the 'glutamate hypothesis' of psychotic illness.

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Expression analysis of TALE family transcription factors during avian development

Coy

Borycki

2010

Developmental Dynamics

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The TALE family of homeodomain containing transcription factors consists of the Meis, Prep and Tgif, and the Pbx subfamily of proteins. Several TALE orthologues have been identified in amniotes, but no comprehensive analysis of their expression pattern during embryogenesis has been performed. Here, we report on TALE gene expression in the avian embryo. During embryonic development, Pbx genes are predominantly expressed in the neural ectoderm and paraxial mesoderm, although Pbx3 is restricted to the intermediate and lateral mesoderm, and anterior central nervous system. Members of the Meis, Prep, and Tgif subfamilies are expressed at high levels in the paraxial mesoderm, and display differential expression along the anterior-posterior and dorsoventral axes of the developing neural tube. Overall the expression patterns reported in this study are consistent with the known function of the TALE gene family in controlling early patterning of limb, neural tube and paraxial mesoderm tissues during embryogenesis.

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Prep2: Cloning and expression of a new prep family member

Cited by 29 publications

References 43 publications

Subcellular Localization of Multiple PREP2 Isoforms Is Regulated by Actin, Tubulin, and Nuclear Export

Subcellular Localization of Multiple PREP2 Isoforms Is Regulated by Actin, Tubulin, and Nuclear Export

Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder

Expression analysis of TALE family transcription factors during avian development

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