CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

Zhu, Quan; Gregg, Keqin; Lozano, Mary M.; Liu, Jinqi; Dudley, Jaquelin P.

doi:10.1128/jvi.74.14.6348-6357.2000

Cited by 33 publications

(73 citation statements)

References 72 publications

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“…CDP belongs to a family of proteins whose role as a transcriptional repressor has been demonstrated in a number of systems (13,26,27). On the basis of our earlier studies of the cell type distributions of SATB1 and CDP and their interaction with the L2a element (16,17), we hypothesized that SATB1 and CDP play positive and negative roles, respectively, in CD8␣ gene regulation.…”

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confidence: 99%

A Role for SATB1, a Nuclear Matrix Association Region-Binding Protein, in the Development of CD8SP Thymocytes and Peripheral T Lymphocytes

Nie

Maika

Tucker

et al. 2005

The Journal of Immunology

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Studies have suggested that binding of the SATB1 protein to L2a, a matrix association region located 4.5 kb 5′ to the mouse CD8α gene, positively affects CD8 expression in T cells. Therefore, experiments were performed to determine the effect on T cell development of reduced expression of SATB1. Because homozygous SATB1-null mice do not survive to adulthood due to nonthymus autonomous defects, mice were produced that were homozygous for a T cell-specific SATB1-antisense transgene and heterozygous for a SATB1-null allele. Thymic SATB1 protein was reduced significantly in these mice, and the major cellular phenotype observed was a significant reduction in the percentage of CD8SP T cells in thymus, spleen, and lymph nodes. Mice were smaller than wild type but generally healthy, and besides a general reduction in cellularity and a slight increase in surface CD3 expression on CD8SP thymocytes, the composition of the thymus was similar to wild type. The reduction in thymic SATB1 does not lead to the variegated expression of CD8-negative single positive thymocytes seen upon deletion of several regulatory elements and suggested by others to reflect failure to activate the CD8 locus. Thus, the present results point to an essential role for SATB1 late in the development and maturation of CD8SP T cells.

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confidence: 99%

A Role for SATB1, a Nuclear Matrix Association Region-Binding Protein, in the Development of CD8SP Thymocytes and Peripheral T Lymphocytes

Nie

Maika

Tucker

et al. 2005

The Journal of Immunology

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“…The silencer CDP, the mammalian homolog of the Drosophila CUT protein and a homeoprotein, negatively regulates HPV-dependent transcription by binding to specific DNA elements located in the viral promoters and long control regions, thus repressing HPV replication (22)(23)(24). In addition, CDP has been shown to block the transcription of mouse mammary tumor viruses through binding to the negative regulatory regions located in the long terminal repeats of mouse mammary tumor virus (25)(26)(27).…”

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confidence: 99%

PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter

Chao

Harada

Hyndman

et al. 2004

Journal of Biological Chemistry

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Cellular homeoproteins have been shown to regulate the transcription of several viruses, including herpes simplex viruses, human papillomaviruses, and mouse mammary tumor viruses. Previous studies investigating the anti-viral mechanisms of several cyclin-dependent kinase inhibitors showed that the homeoproteins, pre B-cell leukemia transcription factor 1 (PBX1) and PBXregulating protein-1 (PREP1), function as transcriptional activators of Moloney murine leukemia virus. Here, we examined the involvement of cellular homeoproteins in regulating the activity of the human cytomegalovirus immediate early (CMV IE) promoter. We identified a 45-bp element located at position ؊593 to ؊549 upstream of the transcription start site of the CMV IE gene, which contains multiple putative homeoprotein binding motifs. Gel shift assays demonstrated the physical association between a homeodomain protein, pancreatic-duodenal homeobox factor-1 (PDX1) and the 45-bp cytomegalovirus (CMV) region. We further determined that PDX1 represses the CMV IE promoter activity in 293 cells. Overexpression of PDX1 resulted in a decrease in transcription of the CMV IE gene. Conversely, blocking PDX1 protein synthesis and mutating the PDX1 binding sites enhanced CMV IE-dependent transcription. Collectively, our results represent the first work demonstrating that a cellular homeoprotein, PDX1, may be a repressor involved in regulation of human CMV gene expression. Cyclin-dependent kinases (CDKs)1 are key regulators of cell cycle control and transcription, which represent attractive targets for cancer therapy. Two CDK inhibitors (CDKIs), flavopiridol and UCN-1, are currently in clinical trials as potential anti-cancer therapeutics (1, 2). Previous studies also have shown the viral inhibitory effects of several CDKIs, including flavopiridol, purvalanol A, roscovitine, olomoucine, and 5,6-dichloro-1-␤-D-ribofuranosylbenzimidazole, on human immunodeficiency virus, herpes simplex virus (HSV), and Moloney murine leukemia virus (MLV) infection (3-6). Interestingly, all of these anti-viral CDKIs target CDK7 or CDK9, which are required for cellular transcription (5, 7-9).It has been hypothesized that the CDKIs block viral replication by inhibiting the transcription of specific cellular genes that are required for viral infection. Our previous work tested this hypothesis using microarray technology and identified a cellular homeoprotein, pre B-cell leukemia transcription factor 1 (PBX1), as a target of the CDKIs and a required cellular co-factor for Moloney MLV replication (3). PBX1 was shown to form a heterodimer with another homeodomain protein, PBXregulating protein-1 (PREP1), and function as a transcriptional activator of Moloney MLV (3). The PBX1-PREP1 DNA binding motif, TGATTGAC, was further shown to be conserved in the long terminal repeats of 14 other murine retroviruses (3), suggesting the importance of homeoproteins in regulating retroviral transcription.A number of cellular homeoproteins, including OCT-1, Brn3a, and Brn-3b, as well as CCAAT displaceme...

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“…1D) showed a drastic reduction of reporter activity in TGF-␤-treated cells, a finding in agreement with a published report on endogenous (Mtv-2) transcripts (12). Only the Dex-induced level could be measured: with this assay, the basal level in mammary cells, in contrast to B cells, is exceedingly low and below detection due to negative regulatory factors (71). A strong negative effect of TGF-␤ was also observed with an LTR truncated at position Ϫ303 or mutated in both GABP-binding sites.…”

Section: Resultsmentioning

confidence: 99%

Transforming Growth Factor β Enhances the Glucocorticoid Response of the Mouse Mammary Tumor Virus Promoter through Smad and GA-Binding Proteins

Aurrekoetxea-Hernández

Buetti

2004

J Virol

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Tissue-specific transcription is advantageously investigated by using viral promoters, which are selected for compact regulatory elements. Mouse mammary tumor virus (MMTV) has adapted to specialized cell types and targets initially B lymphocytes. We previously showed that, in B-cell lines, glucocorticoid-induced MMTV transcription requires an ETS family factor, GA-binding protein (GABP), bound in tandem to the MMTV DNA next to the glucocorticoid receptor (GR). We now report that transforming growth factor ␤ (TGF-␤) superinduces this response up to 10-fold through binding of its effectors, Smads, between the GABP-binding motifs. The basal level was unaffected. The TGF-␤-glucocorticoid cooperation also depended on GR and GABP binding, was transferable to another promoter, and occurred both with transiently transfected and with integrated templates. Smad3 associated in vitro with GR, with GABP␣ (via the MH2 domain), and with GABP␤, Smad4 only with GABP␣. Interactions of Smad3 with GABP (when coexpressed or endogenous to B cells) were shown by coprecipitation and by mammalian two-hybrid assay. This composite DNA element integrates three signaling pathways deriving from TGF-␤, glucocorticoid hormones, and a unique ETS factor, and may allow MMTV to exploit factors from the milk. It may as well indicate novel possibilities for cellular regulatory networks.

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CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

Abstract: Mouse mammary tumor virus (MMTV) transcription is highest in the lactating

Cited by 33 publications

References 72 publications

A Role for SATB1, a Nuclear Matrix Association Region-Binding Protein, in the Development of CD8SP Thymocytes and Peripheral T Lymphocytes

A Role for SATB1, a Nuclear Matrix Association Region-Binding Protein, in the Development of CD8SP Thymocytes and Peripheral T Lymphocytes

PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter

Transforming Growth Factor β Enhances the Glucocorticoid Response of the Mouse Mammary Tumor Virus Promoter through Smad and GA-Binding Proteins

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