Genetic Relationships of the Genes Encoding the Human Proteasome β Subunits and the Proteasome PA28 Complex

McCusker, Derek; Jones, Tania; Sheer, Denise; Trowsdale, John

doi:10.1006/geno.1997.4948

Cited by 14 publications

(10 citation statements)

References 36 publications

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“…The locus includes several MHC-II homologous pseudogenes that represent defunct duplications of ancient MHC-II genes (29). Also within the locus are five genes that do not bear structural homology to MHC-II proteins, the TAP1 and TAP2 genes involved in peptide transport for MHC-I antigen presentation, the proteasome 20s core beta subunit genes PSMB8 and PSMB9, and the bromodomain and extra terminal domain transcriptional regulator gene BRD2 (25,38,67).…”

mentioning

confidence: 99%

CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

Majumder

Boss

2010

Molecular and Cellular Biology

120

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The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divide the MHC-II locus into apparent evolutionary domains were identified. To define the role of CTCF in mediating regulation of the MHC II genes, chromatin conformation capture assays, which provide an architectural assessment of a locus, were conducted across the MHC-II region. Depending on whether MHC-II genes and the class II transactivator (CIITA) were being expressed, two CTCF-dependent chromatin architectural states, each with multiple configurations and interactions, were observed. These states included the ability to express MHC-II gene promoter regions to interact with nearby CTCF sites and CTCF sites to interact with each other. Thus, CTCF organizes the MHC-II locus into a novel basal architecture of interacting foci and loop structures that rearranges in the presence of CIITA. Disruption of the rearranged states eradicated expression, suggesting that the formation of these structures is key to coregulation of MHC-II genes and the locus.Spanning nearly 700 kb of the short arm of chromosome 6 at 6p21.31, the major histocompatibility complex class II (MHC-II) locus contains a dense cluster of highly polymorphic genes that encode the alpha and beta chains of the classical MHC-II heterodimeric molecules (reviewed in references 8, 21, and 59). Three MHC-II isotypes, HLA-DR, -DQ, and -DP, can be formed, and they present antigenic peptides to CD4 T lymphocytes in order to initiate, control, and/or maintain adaptive immune responses (20). This antigen presentation process is aided by two MHC-II region-encoded molecules, HLA-DM and HLA-DO, which are also alpha/beta heterodimers with sequence and structural homology with MHC-II proteins (55, 64). The locus includes several MHC-II homologous pseudogenes that represent defunct duplications of ancient MHC-II genes (29). Also within the locus are five genes that do not bear structural homology to MHC-II proteins, the TAP1 and TAP2 genes involved in peptide transport for MHC-I antigen presentation, the proteasome 20s core beta subunit genes PSMB8 and PSMB9, and the bromodomain and extra terminal domain transcriptional regulator gene BRD2 (25,38,67).MHC-II genes are expressed in B lymphocytes, macrophages, and dendritic cells and certain cells within the thymus. Gamma interferon (IFN-␥) is a potent inducer of MHC-II gene expression in most cell types (12). The transcription factors RFX (regulatory factor X), CREB (cyclic AMP [cAMP] response element binding protein), and NF-Y (nuclear factor Y) are constitutively and ubiquitously expressed and bind to highly conserved MHC-II gene-and related gene promoterproximal sequences termed the X1, X2, and Y boxes (9, 51, 59). CIITA (class II transactivator) interacts with the X-Y box-bound factors and mediates the i...

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confidence: 99%

CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

Majumder

Boss

2010

Molecular and Cellular Biology

120

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“…The UBE3A gene encodes the E6-AP ubiquitin-protein ligase, which functions in protein ubiquitination and has been shown to be mutated in Angelman syndrome patients (Kishino et al, 1997). PSMB4 is a subunit of PA28 proteasome activator and proteasome is responsible for degradation of short lived and misfolded cytosolic and nuclear proteins in cells (McCusker et al, 1997). As suggested by Venkitaraman, the involvement of BRCA1 in ubiquitin-mediated protein degradation could help to explain the multiplicity of biological roles ascribed to this protein, including coordination of DNA repair-related events (Venkitaraman, 2002).…”

Section: Identification and Analysis Of Brca1 Induced Genesmentioning

confidence: 99%

Identification of genes induced by BRCA1 in breast cancer cells

Atalay

Crook

Öztürk

et al. 2002

Biochemical and Biophysical Research Communications

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Inherited mutations of the BRCA1 gene predispose to cancer of the breast, ovaries and other organs. The BRCA1 protein product is implicated in the maintenance of chromosomal integrity as BRCA1-deficient cells display gross chromosomal rearrangements. Chromosomal instability in BRCA1-deficient cells is related to inappropriate DNA double-strand break repair. The role of the BRCA1 gene in the maintenance of chromosomal integrity is linked to a number of biological properties of its protein product including transcriptional regulation. The aim of this study is to identify genes that are regulated by BRCA1. Initial attempts to overexpress BRCA1 in breast cancer cells with the tightly-regulated ecdysone inducible system did not result in the desired levels of BRCA1 protein and ectopic BRCA1 expression was therefore performed by using the constitutive expression vector. In this study, we have identified genes whose expression levels are upregulated as a result of BRCA1 overexpression in MCF7 breast carcinoma cells by using the suppression subtractive hybridisation (SSH) method. Differential screening, sequencing and homology search studies showed that BRCA1 overexpression in breast cancer cells leads to transcriptional upregulation of distinct classes of genes encoding proteins involved in cellular processes such as DNA repair, chromosome assembly and segregation, signal transduction, RNA surveillance, ubiquitin-mediated proteolysis, amino acid transport, RNA metabolism and glucose metabolism. This study is the first to report BRCA1-

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“…The genes coding for the PA28‐α, PA28‐β and PA28‐γ subunits, PSME1 , PSME2 and PSME3 , respectively, have all been identified and mapped in both humans and mice [16–19]. Similarity in sequence and gene organization indicate that the genes are related evolutionarily to one another [17, 19].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In both humans and mice, the PSME1 and PSME2 genes are tightly linked (the distance between them being less than 40 kb) and are closely linked to the PSMB5 gene which in humans is located on chromosome 14 [16, 19]. The physical association of the IFN‐γ‐inducible PSME genes with PSMB5 , a paralogous gene to PSMB8 found in the Mhc , has been interpreted as evidence that the ancestral PSME gene was associated with the Pre‐Mhc complex [16, 18]. Based on the identification of regions on the human chromosomes 1, 9 and 19 paralogous to the Mhc region [21, 22], Kasahara and coworkers [21] hypothesized that the Pre‐Mhc region contained three tandemly arranged PSMB housekeeping genes, pre‐PSMB5 , pre‐PSMB6 and pre‐PSMB7 .…”

Section: Introductionmentioning

confidence: 99%

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Identification and Linkage of the Proteasome Activator Complex PA28 Subunit Genes in Zebrafish

2000

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PA28 is an activator of the latent 20S proteasome, a large multisubunit complex involved in intracellular proteolysis. Two forms of hexameric PA28 have been identified, PA28-(alphabeta)3 and PA28-(gamma)6, of which the former is of immunological importance. Both the PA28-alpha and PA28-beta subunits are inducible by interferon-gamma (IFN-gamma) and the PA28-(alphabeta)3 complex enhances the ability of the 20S proteasome to produce peptides suited for binding to major histocompatibility complex (Mhc) class I molecules. To identify the homologues of the PA28 subunits in zebrafish we screened a cDNA library and obtained full-length cDNA sequences of the genes PSME1, PSME2 and PSME3 coding for the PA28-alpha, PA28-beta and PA28-gamma subunits, respectively. Phylogenetic analysis indicates the existence of the ancestors of all three genes prior to the divergence of tetrapods and bony fishes. The IFN-gamma-inducible subunits, PA28-alpha and PA28-beta, evolve faster than the presumably older PA28-gamma subunit. Using zebrafish radiation hybrid panels, the genes PSME2 and PSME3 were mapped to linkage group 12 and shown to be separated by a distance of less than 2.4 cM. This observation suggests that an intrachromosomal duplication event created the precursor of the IFN-gamma-inducible genes from a PA28-gamma-like ancestor prior to their recruitment into the Mhc class I peptide presentation pathway.

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Genetic Relationships of the Genes Encoding the Human Proteasome β Subunits and the Proteasome PA28 Complex

Cited by 14 publications

References 36 publications

CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

Identification of genes induced by BRCA1 in breast cancer cells

Identification and Linkage of the Proteasome Activator Complex PA28 Subunit Genes in Zebrafish

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