THE INDUCTION OF CLASS I AND II MAJOR HISTOCOMPATIBILITY COMPLEX BY ALLOGENEIC STIMULATION IS DEPENDENT ON THE TRANSCRIPTION FACTOR INTERFERON REGULATORY FACTOR 1 (IRF-1)

1996 ◽  
Vol 62 (12) ◽  
pp. 1895-1901 ◽  
Author(s):  
Michael Hobart ◽  
Vido Ramassar ◽  
Nelson Goes ◽  
Joan Urmson ◽  
Philip F. Halloran
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Interferon Regulatory Factor ◽  
Class I ◽  
Major Histocompatibility ◽  
Regulatory Factor ◽  
Histocompatibility Complex ◽  
Interferon Regulatory Factor 1 ◽  
Allogeneic Stimulation

scholarly journals A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes.

1990 ◽  
Vol 10 (8) ◽  
pp. 4100-4109 ◽  
Author(s):  
U Henseling ◽  
W Schmidt ◽  
H R Schöler ◽  
P Gruss ◽  
A K Hatzopoulos
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cell Lines ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mouse Tissues ◽  
I Gene

AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2Kk molecules correlates with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2Kk gene failed to activate transcription in H-2Kk-negative cells. Examination of the proteins interacting with the H-2Kk enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of beta 2-microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.

scholarly journals Human Cytomegalovirus Protein US11 Provokes an Unfolded Protein Response That May Facilitate the Degradation of Class I Major Histocompatibility Complex Products

2005 ◽  
Vol 79 (5) ◽  
pp. 2768-2779 ◽  
Author(s):  
Boaz Tirosh ◽  
Neal N. Iwakoshi ◽  
Brendan N. Lilley ◽  
Ann-Hwee Lee ◽  
Laurie H. Glimcher ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Unfolded Protein Response ◽  
Human Cytomegalovirus ◽  
Dominant Negative ◽  
Class I ◽  
Major Histocompatibility ◽  
Unfolded Protein ◽  
Histocompatibility Complex ◽  
Protein Response

ABSTRACT The human cytomegalovirus (HCMV) glycoprotein US11 diverts class I major histocompatibility complex (MHC) heavy chains (HC) from the endoplasmic reticulum (ER) to the cytosol, where HC are subjected to proteasome-mediated degradation. In mouse embryonic fibroblasts that are deficient for X-box binding protein 1 (XBP-1), a key transcription factor in the unfolded protein response (UPR) pathway, we show that degradation of endogenous mouse HC is impaired. Moreover, the rate of US11-mediated degradation of ectopically expressed HLA-A2 is reduced when XBP-1 is absent. In the human astrocytoma cell line U373, turning on expression of US11, but not US2, is sufficient to induce a UPR, as manifested by upregulation of the ER chaperone Bip and by splicing of XBP-1 mRNA. In the presence of dominant-negative versions of XBP-1 and activating transcription factor 6, the kinetics of class I MHC HC degradation were delayed when expression of US11 was turned on. The magnitude of these effects, while reproducible, was modest. Conversely, in cells that stably express high levels of US11, the degradation of HC is not affected by the presence of the dominant negative effectors of the UPR. An infection of human foreskin fibroblasts with human cytomegalovirus induced XBP-1 splicing in a manner that coincides with US11 expression. We conclude that the contribution of the UPR is more pronounced on HC degradation shortly after induction of US11 expression and that US11 is sufficient to induce such a response.

scholarly journals A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes

1990 ◽  
Vol 10 (8) ◽  
pp. 4100-4109
Author(s):  
U Henseling ◽  
W Schmidt ◽  
H R Schöler ◽  
P Gruss ◽  
A K Hatzopoulos
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cell Lines ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mouse Tissues ◽  
I Gene

AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2Kk molecules correlates with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2Kk gene failed to activate transcription in H-2Kk-negative cells. Examination of the proteins interacting with the H-2Kk enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of beta 2-microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.

scholarly journals Distinct Transcriptional Pathways Regulate Basal and Activated Major Histocompatibility Complex Class I Expression

2003 ◽  
Vol 23 (10) ◽  
pp. 3377-3391 ◽  
Author(s):  
T. Kevin Howcroft ◽  
Aparna Raval ◽  
Jocelyn D. Weissman ◽  
Anne Gegonne ◽  
Dinah S. Singer
Keyword(s):  
Transcription Factor ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Transcription Initiation ◽  
Core Promoter ◽  
Class I ◽  
Major Histocompatibility ◽  
Gene Target ◽  
The Core ◽  
Histocompatibility Complex

ABSTRACT Transcription of major histocompatibility complex (MHC) class I genes is regulated by both tissue-specific (basal) and hormone/cytokine (activated) mechanisms. Although promoter-proximal regulatory elements have been characterized extensively, the role of the core promoter in mediating regulation has been largely undefined. We report here that the class I core promoter consists of distinct elements that are differentially utilized in basal and activated transcription pathways. These pathways recruit distinct transcription factor complexes to the core promoter elements and target distinct transcription initiation sites. Class I transcription initiates at four major sites within the core promoter and is clustered in two distinct regions: “upstream” (−14 and −18) and “downstream” (+12 and +1). Basal transcription initiates predominantly from the upstream start site region and is completely dependent upon the general transcription factor TAF1 (TAFII250). Activated transcription initiates predominantly from the downstream region and is TAF1 (TAFII250) independent. USF1 augments transcription initiating through the upstream start sites and is dependent on TAF1 (TAFII250), a finding consistent with its role in regulating basal class I transcription. In contrast, transcription activated by the interferon mediator CIITA is independent of TAF1 (TAFII250) and focuses initiation on the downstream start sites. Thus, basal and activated transcriptions of an MHC class I gene target distinct core promoter domains, nucleate distinct transcription initiation complexes and initiate at distinct sites within the promoter. We propose that transcription initiation at the core promoter is a dynamic process in which the mechanisms of core promoter function differ depending on the cellular environment.

Sign in / Sign up

Export Citation Format

Share Document