Downregulation of MHC class I expression due to interference with p105-NF kappa B1 processing by Ad12E1A.

Schouten, Govert J.; Eb, A. J. Van Der; Zantema, A.

doi:10.1002/j.1460-2075.1995.tb07136.x

Cited by 42 publications

(34 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The biological role of p50 homodimers appears to be ambiguous. In some experimental systems p50/p50 homodimers activated transcription from promoters with speci®c kB sites (Collart et al, 1990;Fujita et al, 1992Fujita et al, , 1993Kretzschmar et al, 1992;Schouten et al, 1995;Ten et al, 1992). In other experimental systems these homodimers were unable to activate gene transcription (Beg et al, 1992;Franzoso et al, 1992;Kang et al, 1992;Plaksin et al, 1993;Schmitz and Baeuerle, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Among genes positively regulated by p50/p50 homodimers are TNF-alpha, major histocompatibility complex (MHC) class I genes, as well as its own gene nf-kb1 which encodes p50 as well as the inhibitor protein p105 (Collart et al, 1990;Schouten et al, 1995;Ten et al, 1992). There are also data indicating that p50/p50 binds with high a nity to certain kB sites in the promoter region of ikb-a and nf-kb2 genes (Le Bail et al, 1993;Liptay et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Pérez²,

et al. 1999

View full text Add to dashboard Cite

To elucidate the possible role of NF-kB in mouse skin carcinogenesis we studied the expression of p50 (NFkB1), p52 (NF-kB2), p65 (RelA) and IkB-a inhibitor as well as kB-binding activity in adult SENCAR mouse skin, skin papillomas, and squamous cell carcinomas (SCC) generated by a two-stage carcinogenesis protocol. We found that in normal epidermis all of the above proteins were mostly expressed in the cytoplasm of basal cells. Western blot analysis revealed a dramatic increase of p50 and p52 expression in mouse skin tumors starting from the middle stage of promotion. We also found that the level of IkB-a protein in many late papillomas and SCC was lower than in normal epidermis. Results of EMSA showed an increase in kB-binding activity in mouse skin tumors and suggested that p50 is the major component of constitutive kB-binding complexes in normal epidermis and in tumors. It has been shown that nuclear IkB protein Bcl-3 is able to increase p50/p50 homodimer binding to the di erent kB sites in mouse thymocytes. Our ®nding on Bcl-3 overexpression in late papillomas and SCC could explain the selective increase of p50-related kB-binding in mouse skin tumors. Thus, our results strongly suggest the important role of p50 in skin carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Pérez²,

et al. 1999

View full text Add to dashboard Cite

show abstract

“…However, other reports showed that p50 homodimers have the capacity to activate in vivo and in vitro a promoter containing B sites (22,23,31). Moreover, other studies have postulated that the p50 homodimers are involved in regulating the expression of tumor necrosis factor alpha, NF-B1 (p105), and major histocompatibility complex (MHC) class I genes (17,51,55,61), although the surface expression levels of MHC class I molecules in cells of p50 null mice are normal (53). Previous in vitro studies and transient-transfection experiments have shown that Bcl-3 is able to remove p50 homodimers from DNA, thus allowing transcriptional activation to occur through the potent p50-RelA heterodimers (20,21,26,27,34,42,43,64).…”

mentioning

confidence: 99%

Constitutive Expression of Bcl-3 in Thymocytes Increases the DNA Binding of NF-κB1 (p50) Homodimers In Vivo

Caamaño

Pérez

Lira

et al. 1996

Molecular and Cellular Biology

View full text Add to dashboard Cite

Previous studies have indicated that Bcl-3 interacts through its ankyrin repeats with the transcriptional factors NF-B1 (p50) and NF-B2 (p52), affecting their biological activities. To further investigate the role of Bcl-3 in vivo and its association with the NF-B proteins, we have generated transgenic mice constitutively expressing Bcl-3 in thymocytes. The results indicate that Bcl-3 is associated with endogenous p50 and p52 in nuclear extracts from transgenic animals. Remarkably, constitutive expression of Bcl-3 in these cells augments the DNA binding activity of endogenous p50 homodimers more than 10-fold but does not significantly increase the activity of p52 homodimers. This effect could be reproduced in vitro and is blocked by anti-Bcl-3 antibodies. We have also shown that Bcl-3 is phosphorylated in thymocytes and that its dephosphorylation greatly decreases the effect on p50 homodimers.The bcl-3 gene was cloned from a recurrent chromosomal translocation, t(14;19)(q32;q13.1), present in human B-cell chronic lymphocytic leukemias (39,40,60,65). It is remarkable that all the rearrangements in this locus occur in the 5Ј regulatory region of the gene and result in increased expression of wild-type 45,65). This protein contains seven ankyrin repeats and shares structural features with I B␣, I B␤, I B␥, and the C terminus of NF-B2 (5, 24, 57).Members of the Rel/NF-B family of transcription factors play a major role as early mediators of immune and inflammatory responses (4, 37, 54). Members of this family are differentially expressed during mouse embryonic development and in adult lymphoid tissues (13,14,62). Each of these proteins contains a highly conserved region of approximately 300 amino acids called the Rel homology domain which is responsible for both DNA binding and dimerization. In mammalian cells, this protein family can be divided into two classes. One class includes the precursors NF-B1 (p105/p50) and NF-B2 (p100/p52), which are synthesized as inactive molecules and remain in the cytoplasm. These precursors (p105 and p100), upon proteolytic processing, will generate the DNA-binding subunits p50 and p52, respectively. The other class of proteins comprises RelA (p65), c-Rel, and RelB. These proteins do not undergo proteolytic processing, and they harbor transcriptional activation domains (36). The biological functions of p50, RelA, RelB, and c-Rel have recently been addressed by the generation of null mice (7,11,30,53,63).The primary Rel/NF-B transactivating complexes in cells appear to be homo-and heterodimers involving members of each subclass that bind to specific B sites and differ in their transcriptional activities. In unstimulated cells the Rel/NF-B dimers are associated with the inhibitor I B proteins and remain as an inactive pool in the cytoplasm. Upon stimulation by different agents, I B molecules are rapidly phosphorylated and degraded, allowing the NF-B dimers to translocate into the nucleus and regulate transcription through binding to the B sites (2,5,10,18,19,24,36,41,46,(56)(57)(58)(59...

show abstract

“…Therefore, an upstream oligo, U1, corresponding to the RT1.A l sequence, and a downstream oligo, D1, derived from RT16 (24), were used for RT-PCR of total RNA from the Ad5-transformed BRK cell line BXc22, which expresses high levels of RT1-A u (see Fig. 1B) (25). The PCR product of 473 bp was subcloned in the AT vector pCR2.1 (Invitrogen), resulting in PCR2.1-RT1-A u 5Ј.…”

Section: Methodsmentioning

confidence: 99%

Differential Expression of Tapasin and Immunoproteasome Subunits in Adenovirus Type 5- Versus Type 12-transformed Cells

Vertegaal¹,

Kuiperij

Houweling

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Adenovirus type 12 (Ad12)-transformed baby rat kidney (BRK) cells are oncogenic in syngeneic immunocompetent rats in contrast to adenovirus type 5 (Ad5)-transformed BRK cells, which are not oncogenic in these animals. A significant factor contributing to the difference in oncogenicity may be the low levels of major histocompatibility complex (MHC) class I membrane expression in Ad12-transformed BRK cells as compared with those in Ad5-transformed BRK cells, which presumably results in escape from killing by cytotoxic T lymphocytes. Here we show that, in addition to the decreased levels of expression of the MHC class I heavy chain and the peptide transporter Tap-2, the expression levels of the chaperone Tapasin and the immunoproteasome components MECL-1, PA28-␣, and PA28-␤ also are much lower in Ad12-than in Ad5-transformed BRK cells. The low expression levels of these proteins may contribute to the escape from killing by cytotoxic T lymphocytes, because the generation of optimal peptides and loading of these peptides on MHC class I require these components. Increased levels of phosphorylated signal transducer and activator of transcription-1 protein and expression of IFN regulatory factor-7 were found in Ad5-versus Ad12-transformed BRK cells. Therefore, the critical alteration leading to the plethora of differences may be an interferon (-related) effect.

show abstract

Downregulation of MHC class I expression due to interference with p105-NF kappa B1 processing by Ad12E1A.

Cited by 42 publications

References 65 publications

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Constitutive Expression of Bcl-3 in Thymocytes Increases the DNA Binding of NF-κB1 (p50) Homodimers In Vivo

Differential Expression of Tapasin and Immunoproteasome Subunits in Adenovirus Type 5- Versus Type 12-transformed Cells

Contact Info

Product

Resources

About