Impaired transcription of the poly rl:rC- and interferon-activatable 202 gene in mice and cell lines from the C57BU6 strain

Gariglio, Marisa; Panico, Saverio; Cavallo, G; Choubey, Divaker; Lengyel, Péter; Landolfo, Santo

doi:10.1016/0042-6822(92)90300-e

Cited by 31 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition of the NF-B-dependent expression of genes by transfected p202 and also by IFN treatment makes it conceivable that the induction of p202 by IFN contributes to the transiency of the induction of IFN-␤ by poly(rI) ⅐ poly(rC) (69). In mice of the C57BL/6 inbred strain (unlike in mice from several other strains), p202 is not induced by IFN (21). At the same time, infection by some viruses or treatment with poly(rI) ⅐ poly(rC) was reported to induce much more IFN-␣/␤ in C57BL/6 mice than in mice from several other strains (16).…”

Section: Discussionmentioning

confidence: 99%

The Interferon-Inducible p202 Protein as a Modulator of Transcription: Inhibition of NF-κB, c-Fos, and c-Jun Activities

Wang

Ghosh

Lengyel

1996

Molecular and Cellular Biology

147

154

View full text Add to dashboard Cite

The interferons (IFNs) are cytokines with antiviral, antibacterial, antiprotozoal, immunomodulatory, and cell growth-regulatory functions. They exert these functions by controlling the expression of numerous genes encoding effector proteins (16,41,55,65). One set of effector proteins, including p202, p203, p204, and D3, is encoded by six or more structurally related and IFN-activatable murine genes at the q21-q23 region of chromosome 1 (gene 200 cluster) (13,36,42,48,59). Two homologous human proteins (myeloid cell nuclear differentiation antigen [MNDA] and IFI16) have also been described (7, 64). The proteins encoded by all these genes have homologous C-terminal 200-amino-acid segments (42).At least four of the proteins (p202, p204, MNDA, and IFI16) are nuclear (7,11,12,15,42). Upon treatment of cells with IFN, the induced p202 first appears in the cytoplasm, where it is attached to a fast-sedimenting subcellular component, and then accumulates in the nucleus after a delay (12). In metaphase cells, p202 appears to be associated with chromatin. Although p202 binds DNA in vitro, the cleavage of DNA in isolated nuclei does not result in the release of p202. This and other results suggest that the binding of p202 in the nucleus is at least in part due to protein-protein interactions.The proteins found to bind to p202 in vitro and in vivo include the retinoblastoma susceptibility protein pRb (10), which has a central role in controlling cell cycling (68). It is the hypophosphorylated, growth-inhibitory form of pRb that binds to p202. Overexpression of p202 in transfected cells slows down cell proliferation. The contribution of the interaction between p202 and pRb to the cell growth-inhibitory activity of p202 remains to be explored. However, the finding that p202 interacts with pRb prompted us to test whether p202 also interacts with other proteins controlling transcription. Here we describe studies concerning the effect of p202 on the NF-B p50 and p65 and the AP-1 c-Jun and c-Fos transcription factors. (5,56,57,60). The NF-B protein is a heterodimer consisting of two proteins, p50 (also designated NF-B 1 ) and p65 (also designated Rel A). p50 and p65 are members of the Rel/NF-B family of proteins. These proteins serve as inducible eukaryotic transcription factors that form various homo-and heterodimers. NF-B (i.e., the p50-p65 complex) is present in essentially all cells and is the most abundant of the Rel/NF-B family heterodimers. NF-B is retained in an inactive form in the cytoplasm as a consequence of the binding of particular proteins of the IB family (6, 24) (i.e., IB-␣ and IB-␤) (62). The activation of NF-B and its movement to the nucleus can be correlated with the proteolytic degradation of one or both of the IB proteins (8,46,49,60,62,63). This can be triggered by the phosphorylation of these proteins. The long list of agents activating NF-B includes various cytokines (e.g., interleukin-1 and tumor necrosis factor alpha), phorbol esters (e.g., phorbol myristate acetate [PMA] and tetradecanoyl phorbol ace...

show abstract

Section: Discussionmentioning

confidence: 99%

The Interferon-Inducible p202 Protein as a Modulator of Transcription: Inhibition of NF-κB, c-Fos, and c-Jun Activities

Wang

Ghosh

Lengyel

1996

Molecular and Cellular Biology

147

154

View full text Add to dashboard Cite

show abstract

“…This discrepancy between in vivo and in vitro studies is not surprising and can be easily explained by taking into account the Ifi 204 promoter organization containing IFN-responsive sequences that, when cells are cultured in vitro, likely lose their tissue specificity. C57BL/6 mice or their cell lines do not express the 202 mRNA on both poly rI:rC and IFN treatment [32,33]. To verify whether p204 and D3 expression was equally suppressed in these mice after IFN stimulation, resident peritoneal M from both DBA/2 and C57BL/6 mice were stimulated in vitro for 24 h with IFN-␣, IFN-␥, or LPS.…”

Section: Resultsmentioning

confidence: 99%

The murine homolog of the HIN 200 family, Ifi 204, is constitutively expressed in myeloid cells and selectively induced in the monocyte/macrophage lineage

Gariglio

Andrea²,

Lembo³

et al. 1998

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

“…I® 204, another member of the I® 200 gene cluster, encodes a 72 kDa phosphoprotein (p204), that increases several-fold upon IFN-treatment and translocates into the nucleus Hertel et al, 1999b). p204 is selectively induced in vivo in monocytes/macrophages by IFN inducers, such as the synthetic double-stranded RNA poly rI : rC, or LPS, suggesting a potential role in their functional dierentiation (Gariglio et al, 1992.…”

Section: Introductionmentioning

confidence: 99%

“…The bestcharacterized member is I® 202. It encodes a 52 kDa phosphoprotein that increases 20 ± 30-fold in both cultured cells and in vivo tissues in response to IFN-a (Gariglio et al, 1992(Gariglio et al, , 1994, and translocates into the nucleus, where it binds to pRb and some transcription factors such as E2F, p53, AP-1, c-Fos, c-Jun. NFkB, MyoD and UBF1 (Min et al, 1996;Choubey et al, 1995Choubey et al, , 1996Datta et al, 1998;Liu et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The retinoblastoma protein is an essential mediator that links the interferon-inducible 204 gene to cell-cycle regulation

Hertel

Rolle²,

Andrea

et al. 2000

Oncogene

Self Cite

View full text Add to dashboard Cite

We have previously demonstrated that overexpression of p204, a member of the I® 200 gene family, inhibits growth, delays G0/G1 progression into S phase, and impairs E2F-mediated transcriptional activity. In this study, we show that p204 directly binds the retinoblastoma protein (pRb) in vivo to exert its activity. Transient p204 overexpression in Rb+/+ mouse embryo ®bro-blasts (MEF) inhibits cell proliferation, but does not aect cell growth in MEF derived from Rb7/7 mice. Two human cell lines, Saos2 and C33A, bearing an inactive pRb, but not primary human embryo ®broblasts, are resistant to the p204 antiproliferative activity. p204 contains two 200 amino acid motifs, designated as type a or b domains, each containing a canonical Rb binding motif (LXCXE). When dominant-negative mutants at the Rb binding motif were transfected in Rb+/+ MEF, p204 lost its ability to inhibit cell growth, delay cell transition from G1 to S phase, and impair DNA synthesis. Moreover p204 overexpression in Rb+/+ MEF led to a signi®cant decrease of both DHFR and PCNA proteins, two S phase markers. By contrast, this eect was not observed when Rb+/+ MEF were transfected with a p204 mutated at both Rb binding sites. Finally, overexpression of the LXCXE p204 mutant rendered Rb+/+ MEF resistant to the IFN-a antiproliferative activity, in comparison to the untransfected Rb+/+ MEF. As expected, Rb7/7 cells were unsensitive to the IFN-a induced growth inhibition. Taken as a whole, these results suggest that (i) p204 contributes to the IFN-a antiproliferative activity and (ii) the primary target of p204 leading to ecient G1 arrest as well as to blockade of DNA replication from G1 phase is the pRb regulatory system. Oncogene (2000) 19, 3598 ± 3608.

show abstract

Impaired transcription of the poly rl:rC- and interferon-activatable 202 gene in mice and cell lines from the C57BU6 strain

Cited by 31 publications

References 30 publications

The Interferon-Inducible p202 Protein as a Modulator of Transcription: Inhibition of NF-κB, c-Fos, and c-Jun Activities

The Interferon-Inducible p202 Protein as a Modulator of Transcription: Inhibition of NF-κB, c-Fos, and c-Jun Activities

The murine homolog of the HIN 200 family, Ifi 204, is constitutively expressed in myeloid cells and selectively induced in the monocyte/macrophage lineage

The retinoblastoma protein is an essential mediator that links the interferon-inducible 204 gene to cell-cycle regulation

Contact Info

Product

Resources

About