Intranuclear distribution of the human myeloid cell nuclear differentiation antigen in HL‐60 cells

Abstract

Based on solubility properties, the human myeloid cell nuclear differentiation antigen exists as at least two distinct populations. Most is easily extracted from isolated nuclei in 0.35 M NaCl, while 20 percent resists such treatment. Compared to undigested nuclei, both the amount of myeloid cell nuclear differentiation antigen (MNDA) released from nuclei after DNase I treatment and the amount resisting further extraction in 0.35 M NaCl increased after DNA was digested with DNase I. Under these conditions, there was a concomitant decrease in the amount of MNDA that was extractable with 0.35 M NaCl. Mixing nuclear protein extracts that contain MNDA with nuclei from cells that do not express this protein demonstrated that the MNDA redistributes from the freely soluble form to the nuclear residual fraction as a consequence of DNase I digestion. These data are consistent with a model in which the amount of MNDA that is tightly bound to salt-washed nuclei is held constant in the presence of an excess of unassociated MNDA in the nucleus, and that the level of MNDA binding to this nuclear fraction increases in proportion to the extent of DNA damage resulting from DNase I digestion.

Transcription and Growth Regulatory Functions of the HIN-200 Family of Proteins

“…The size of the spacer region in IFI 16 is regulated by mRNA splicing and can contain one, two, or three copies of a highly conserved 56-amino-acid S/T/P domain encoded by distinct exons (23). In contrast, MNDA, AIM-2, p203, and D3 contain only one 200-amino-acid domain (3,17,18,20). The amino acid composition of the A domains expressed in different HIN-200 proteins is highly conserved, as are the B domains expressed in different family members.…”

“…The HIN-200 family of proteins consists of a number of highly homologous human and murine proteins with similar primary amino acid sequences and biological characteristics. The human HIN-200 family members include IFI 16 (39), the myeloid nuclear differentiation antigen (MNDA) (2,18), and AIM-2 (absent in melanoma) (17), while the mouse HIN-200 family members include p202 (3), p203 (20), p204 (3), and D3 (38). There are a number of reviews that elegantly outline the biochemical characteristics of these proteins and their patterns of expression (15,27,30).…”

The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations

“…IFI 16 shares a common structure (the hallmark of which is a reiterated 200 amino acid domain) with the myeloid cell nuclear differentiation antigen (MNDA), originally described as a differentiation-associated nucleoprotein present in late myeloid precursors and mature myeloid cells [15][16][17]. Because of their restricted tissue distribution [13,14], DNA binding [14], and IFN-inducibility, it has been proposed that MNDA and IFI 16 may act as transcriptional activators/repressors in the myeloid lineage [14,16,17]. The domain organization of IFI 16 and MNDA is also shared by a family of IFN-inducible genes on mouse chromosome 1, the Gene 200 complex [18].…”

Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16

“…The human HIN-200 members include IFI 16 (Trapani et al, 1992), the myeloid nuclear di erentiation antigen (MNDA) (Burrus et al, 1992;Duhl et al, 1989) and AIM-2 (Absent In Melanoma) (DeYoung et al, 1997) while the mouse members include p202 (Choubey et al, 1989), p203 (Gribaudo et al, 1997), p204 (Choubey et al, 1989) and D3 (Tannenbaum et al, 1993). proteins share common structural and biochemical properties including the presence of at least one common 200 amino acid repeat motif of unknown function, the ability to bind double stranded DNA, and all are localized to the nucleus (Dawson and Trapani, 1996;Lengyel et al, 1995;Landolfo et al, 1998;Johnstone and Trapani, 1999).…”