Disease relevance of Hbb-bh1

• Two RING finger proteins, the oncoprotein PML and the arenavirus Z protein, colocalize with the nuclear fraction of the ribosomal P proteins [1].
• A similar result was observed with a Z protein from another arenavirus, Lassa virus, suggesting that this is a general feature of the Arenaviridae [2].
• Here we propose that PML reduces LCMV transcription through its interaction with the Z protein [3].
• We previously showed that hybrid gene constructs of the human fetal G gamma- or mouse embryonic beta h1-globin promoter linked to the viral simian virus 40 T antigen (G gamma/T and beta h1/T) expressed appropriately in embryonic erythroid tissue, with some unexpected expression elsewhere [4].
• Alteration of additional factors other than accumulation of Z protein, for example inactivation of the endogenous mouse genes or some environmental challenge, might produce a mouse model with more relevance to neonatal liver disease [5].

High impact information on Hbb-bh1

• However, in this study, we demonstrate that deletion of murine 5' HS3 reduces expression of the linked embryonic epsilon y- and beta H 1-globin genes only minimally in yolk sac-derived erythroid cells and reduces output of the linked adult beta (beta major plus beta minor) globin genes by approximately 30% in adult erythrocytes [6].
• No benzidine-positive cells or beta H1-globin mRNA expression was detected at the primitive streak or neural plate stage of development (E7.5) [7].
• Z RNA contains the same open reading frame as C4 which predicts a protein of 131 amino acids, but antisera to C4 do not interact with epitopes on this protein when it is synthesized by cell-free translation, hence the presence or absence of a Z protein in vivo could not be determined [8].
• Liver injury is caused by the accumulation of alpha(1)-AT mutant Z protein in hepatocytes, which triggers downstream intracellular injury pathways [9].
• The Z protein is a small zinc-binding RING protein with an unknown function which is required for the viral life cycle [10].

Biological context of Hbb-bh1

• The Z protein acts dominantly to overcome the diffuse phenotype observed in several PML mutants [2].
• Transient transfection assays in prostate and adrenocortical tumor-derived cell lines showed that the G gamma-globin promoter is 7-to 10-fold more active than the beta h1-globin promoter [4].

Anatomical context of Hbb-bh1

• The effect of proteolytic enzymes on hair follicles of transgenic mice expressing the lac Z-protein in cells of the bulge region [11].

Associations of Hbb-bh1 with chemical compounds

• Modulation of hepatic heme-binding Z protein in mice by the porphyrogenic carcinogens griseofulvin and hexachlorobenzene [12].

Analytical, diagnostic and therapeutic context of Hbb-bh1

• Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that adult and embryonic globin genes were appropriately regulated, with the exception of beta h1-globin, which continued to be expressed at a very low level [13].
• Immunofluorescence and coimmunoprecipitation studies indicate that the viral Z protein binds the nuclear, but not the cytoplasmic, fraction of P0 [1].
• Accumulation of Z protein has also been demonstrated by immunocytochemistry [5].

References