The Humandead ringer/brightHomolog,DRIL1:cDNA Cloning, Gene Structure, and Mapping to D19S886, a Marker on 19p13.3 That Is Strictly Linked to the Peutz–Jeghers Syndrome

Kortschak, R. Daniel; Reimann, Heike; Zimmer, Michael; Hj, Eyre; Saint, Robert; De, Jenne

doi:10.1006/geno.1998.5259

Cited by 24 publications

(28 citation statements)

References 13 publications

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“…The integrity of the PCR product was confirmed by sequencing both strands. Both the original, cloned cDNA and the full-length cDNA were identical to the published sequence 10 , except for a carboxy-terminal stretch where Gly 7 Ser 3 in the reported sequence (residues 599-608) was replaced by Gly 6 Ser 4 . The significance of this difference, which maps to a non-conserved region, is unknown.…”

Section: Pcr and Construction Of Human And Murine Dril1 Expression Vementioning

confidence: 94%

“…These cDNAs initiated at 162 and 173 base pairs, respectively, downstream of the reported translation start site 10 . In both cDNAs, use of the first subsequent in-frame ATG gives rise to a protein lacking its amino-terminal 58 amino acids.…”

Section: Pcr and Construction Of Human And Murine Dril1 Expression Vementioning

confidence: 99%

“…DNA sequencing of two independent proviral inserts isolated from rescued colonies revealed that they originated from the same human gene, DRIL1 (ref. 10). The murine orthologue of DRIL1, Bright, encodes a B-cell transcription factor that binds to the matrix-associated region (MAR) of the IgH locus 11 .…”

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confidence: 99%

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A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence

et al. 2002

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Primary fibroblasts respond to activated H-RAS V12 by undergoing premature arrest, which resembles replicative senescence 1 . This irreversible 'fail-safe mechanism' requires p19 ARF , p53 and the Retinoblastoma (Rb) family: upon their disruption, RAS V12 -expressing cells fail to undergo senescence and continue to proliferate 1-7 . Similarly, co-expression of oncogenes such as c-MYC or E1A rescues RAS V12 -induced senescence. To identify novel genes that allow escape from RAS V12 -induced senescence, we designed an unbiased, retroviral complementary DNA library screen. We report on the identification of DRIL1, the human orthologue of the mouse Bright and Drosophila dead ringer transcriptional regulators. DRIL1 renders primary murine fibroblasts unresponsive to RAS V12 -induced anti-proliferative signalling by p19 ARF /p53/p21 CIP1 , as well as by p16 INK4a . In this way, DRIL1 not only rescues RAS V12 -induced senescence but also causes these fibroblasts to become highly oncogenic. Furthermore, DRIL1 immortalizes mouse fibroblasts, in the presence of high levels of p16 INK4a . Immortalization by DRIL1, whose product binds the pRB-controlled transcription factor E2F1 (ref. 8), is correlated with induction of E2F1 activity. Correspondingly, DRIL1 induces the E2F1 target Cyclin E1, overexpression of which is sufficient to trigger escape from senescence. Thus, DRIL1 disrupts cellular protection against RAS V12 -induced proliferation downstream of the p19 ARF /p53 pathway. R AS V12 -induced premature senescence resembles replicative senescence, which occurs upon explantation of primary cells and is unrelated to the 'senescence crisis' that is caused by telomere loss. To identify novel genes that allow a bypass of RAS V12 -induced senescence, we designed an unbiased, functional genetic screen. After retrovirus-mediated expression of RAS V12 , more than 99.9% of a primary mouse embryo fibroblast (MEF) population underwent premature senescence, but a few cells escaped (most likely because of endogenous mutations) and continued to proliferate. To reduce this 'background' in the screen, we generated conditionally immortalized MEFs, co-expressing a temperature-sensitive simian virus 40 (SV40) large T mutant 9 and RAS V12

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Section: Pcr and Construction Of Human And Murine Dril1 Expression Vementioning

confidence: 94%

Section: Pcr and Construction Of Human And Murine Dril1 Expression Vementioning

confidence: 99%

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A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence

et al. 2002

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“…ARIDs are present in many proteins, including the yeast SWI1 protein (Peterson and Herskowitz 1992), the mammalian retinoblastoma binding proteins (RBP1 and RBP2; Fattaey et al 1993), and the mammalian MRF-1 and MRF-2 transcriptional regulators (Huang et al 1996). CFI-1 is most similar to a subset of ARID proteins termed extended ARID (eARID; Kortschak et al 1998) proteins and is the only eARID protein in C. elegans. eARID proteins share additional identities closely flanking the ARID domain and also share similarities in a region C-terminal to the ARID, termed REKLES (Kortschak et al 2000).…”

Section: Cfi-1 Encodes An Arid Transcription Factormentioning

confidence: 99%

Control of neuronal subtype identity by the C. elegans ARID protein CFI-1

Shaham¹,

Bargmann²

2002

Genes Dev.

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The Caenorhabditis elegans hermaphrodite nervous system is composed of 302 neurons that fall into at least 118 diverse classes. Here we describe cfi-1, a gene that contributes to the development of neuronal diversity. cfi-1 promotes appropriate differentiation of the URA sensory neurons and inhibits URA from expressing the male-specific CEM neuronal fate. The UNC-86 POU homeodomain protein is present in CEM and URA neurons, and can promote expression of CEM-specific genes in both CEM and URA, but CFI-1 inhibits expression of these genes in the URA cells. cfi-1 also promotes appropriate differentiation and glutamate receptor expression in the AVD and PVC interneurons. cfi-1 encodes a conserved neuron-and muscle-restricted DNA-binding protein containing an A/T rich interaction domain (ARID). ARID proteins regulate early patterning and muscle fate in Drosophila, but they have not previously been implicated in the control of neuronal subtype identity. In the mammalian nervous system thousands of cell types can be distinguished based on position, gene expression, connectivity, and function. Even in the nematode Caenorhabditis elegans, where the nervous system is composed of only 302 neurons, these can be divided into at least 118 different classes (Sulston and Horvitz 1977;Sulston et al. 1983;White et al. 1986). How is this multitude of neuron types generated? Studies in mammals and in C. elegans suggest that lineage-intrinsic mechanisms are important for the generation of this diversity. Transcriptional regulators that are induced during early development play key roles in determining neuronal subtype identity (Sengupta and Bargmann 1996;Tanabe and Jessell 1996), and are expressed in complex, overlapping patterns.The expression of a particular repertoire of neuronspecific proteins results from the integration of functions of multiple transcription factors. In one well-characterized example, the hermaphrodite-specific neuron (HSN) of C. elegans, which regulates egg-laying, integrates inputs from the position of the cell, the sex of the animal, and its developmental state to achieve its terminally differentiated fate. These cues control HSN differentiation by regulating the expression of an assortment of specific transcriptional regulators. The HSN is born in the tail region of the animal (Sulston et al. 1983), and during embryogenesis its identity is specified, in part, by the tail-restricted homeodomain protein EGL-5 (Desai et al. 1988;Chisholm 1991). Appropriate expression of EGL-5 then allows the HSN to migrate from its early posterior position to its final medial position in the animal. At roughly the same time, the sex-determination pathway, in the form of the zinc-finger transcription factor TRA-1, regulates expression of the programmed cell death gene egl-1 to promote HSN survival in hermaphrodites and death in males (Conradt and Horvitz 1999). In the fourth larval stage (L4), inputs from genes that control developmental timing, such as the period-related gene lin-42, promote HSN terminal differentiation. The...

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“…Database search revealed E2FBP1 to be identical to an AT-rich interaction domain (ARID) family DNA-binding protein, hDril1, which was isolated as a human orthologue of the mouse B-cell regulator of IgH transcription, Bright, and the Drosophila dead ringer protein, Dri. 2 These close homologues of E2FBP1/hDril1 (hereafter, simplified to 'E2FBP1') share a highly homologous ARID with extended flanking regions (eARID). Although few functional overlap has been reported, eARID family proteins are appreciated for their essential roles in the regulation of species and/or cell type-specific responses.…”

Section: Introductionmentioning

confidence: 99%

E2FBP1/hDril1 modulates cell growth through downregulation of promyelocytic leukemia bodies

et al. 2004

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Promyelocytic leukemia nuclear bodies (PML-NBs) comprise multiple regulatory factors and play crucial roles in the maintenance of cellular integrity, while unregulated activation of PML-NBs induces death and premature senescence. Hence, the function of PML-NBs must be directed properly; however, the mechanism that regulates PML-NBs remains unclear. In this paper, we show that PML-NBs are disintegrated by an AT-rich interaction domain family protein E2FBP1/hDril1 through specific desumoylation of promyelocytic leukemia protein (PML) in vivo and in vitro. RNA interference-mediated downregulation of E2FBP1/hDril1 results in hyperplasis of PML-NBs and consequent commitment to PML-dependent premature senescence. Thus, the function of E2FBP1/hDril1 is required for maintenance of survival potential of the cells. Our data suggest a novel mechanism to govern cellular integrity through the modulation of nuclear depots.

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The Humandead ringer/brightHomolog,DRIL1:cDNA Cloning, Gene Structure, and Mapping to D19S886, a Marker on 19p13.3 That Is Strictly Linked to the Peutz–Jeghers Syndrome

Cited by 24 publications

References 13 publications

A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence

A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence

Control of neuronal subtype identity by the C. elegans ARID protein CFI-1

E2FBP1/hDril1 modulates cell growth through downregulation of promyelocytic leukemia bodies

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