Cloning and expression of the human myeloid cell nuclear differentiation antigen: Regulation by interferon α

Abstract

The human myeloid cell nuclear differentiation antigen (MNDA) is a protein of 406 amino acids that is expressed specifically in granulocytes, monocytes and earlier stage cells of these lineages. Degenerate oligonucleotides that could encode regions of MNDA amino acid sequence were used to amplify the MNDA cDNA sequence using the polymerase chain reaction. The amplified cDNA product was sequenced to confirm that it encoded the MNDA protein. It was then used as a probe to isolate five clones from a human bone marrow lambda gt10 cDNA library. A clone containing a 1,672 base pair cDNA insert was sequenced and found to encode the entire MNDA open reading frame, as well as 5' and 3' untranslated regions. The primary structure of the MNDA contains extensive regions of sequence similarity with the protein products of the interferon-inducible genes: 204 and interferon regulatory factor 2. In addition, a 12-base sequence matching the interferon-stimulated response element consensus sequence [GAAAN(N)GAAA] is located in the 5' untranslated region of the MNDA cDNA. The 1.8 kb MNDA mRNA was detected only in cells that express the antigen and the level of MNDA mRNA was elevated in cells treated with either recombinant or natural interferon alpha. The MNDA mRNA was not induced by interferon alpha in cells that do not exhibit a constitutive level of the MNDA mRNA. The MNDA contains sequence motifs found in gene regulatory proteins. The expression and the primary structure of the MNDA indicates that it plays a role in the granulocyte/monocyte cell-specific response to interferon.

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 level of MNDA mRNA in primary monocytes is very low and it is up-regulated at 6 h after the addition of IFN-␣ [15,18]. By contrast, the level of MNDA mRNA in primary granulocytes is unaffected by addition of IFN-␣ and other agents including IFN-␥, LPS, poly rI:rC, and N-formyl-methionyl-leucyl-phenylalanine.…”

“…Three human proteins, myeloid nuclear differentiation antigen (MNDA) [15], IFI 16 [16], and AIM2 (absent in melanoma 2) [17], have been shown to have a putative domain structure with patchy similarity to murine p200 proteins. These human counterparts are primarily nuclear and contain one or two analogous 200-amino acid domains that are imperfect copies.…”

Dysregulated Human Myeloid Nuclear Differentiation Antigen Expression in Myelodysplastic Syndromes: Evidence for a Role in Apoptosis

“…The MNDA rat monoclonal antibody 3C1 was used in previous studies to document cell-specific expression (14)(15)(16)(17)(18)(19) and was also used to immunoaffinity purify MNDA for sequence analysis (20). The monoclonal antibody 3C1 (Chemicon International, Inc. Temecula, CA) was used in all immunochemical assays of MNDA expression.…”

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

“…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).…”

“…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).…”