Mouse anti-Human ARIH2 monoclonal antibody, clone 2D4

Chromosomal translocations involving the MLL1 gene characterize a poor prognosis subset of acute myeloid leukemia (AML), referred to as 11q23-AML. Transcription of the HOXA9 and HOXA10 genes is enhanced in hematopoietic stem and progenitor cells in these leukemias. We previously found the ARIH2 gene was repressed by HoxA9 in myeloid progenitors, but activated by HoxA10 during granulopoiesis. ARIH2 encodes the Triad1 protein, an anti-proliferative E3 ubiquitin ligase. In the current study, we investigate the role of Triad1 in leukemogenesis induced by an MLL1 fusion protein (Mll-Ell). We found Mll-Ell increased expression of HoxA9, HoxA10, and Triad1 because HoxA9 represses only one of two ARIH2 cis elements that are activated by HoxA10. Although Triad1 antagonized the generally pro-proliferative effects of the Mll-Ell oncoprotein, we found blocking HoxA9 and HoxA10 phosphorylation shifted the balance to ARIH2 repression in Mll-Ell(+) cells. We investigated the significance of these in vitro results in a murine bone marrow transplant model. We found Triad1 knockdown significantly shortened the latency to development of AML in mice transplanted with Mll-Ell-transduced bone marrow. And, Triad1 expression fell during the prolonged AML latency period in mice transplanted with bone marrow expressing Mll-Ell alone. Our studies identify Triad1 as a leukemia suppressor in 11q23-AML. This suggests defining relevant Triad1 substrates may indicate novel therapeutic targets in this disease.

Ariadne homolog 2 (ARIH2), as an E3 ubiquitin ligase, is one of the important factors involved in regulating biological functions, such as inflammation and skeletal muscle degeneration. In the present study, the full-length coding sequence of Arih2 gene was cloned from Hy-Line Brown chicken. The tissue transcriptional profiles of Arih2 gene at different developmental stages were detected using quantitative real-time PCR (qRT-PCR), and the Arih2 functional characteristics in immune response were analyzed. The results showed that the full-length coding sequence of Arih2 gene was 1473 bp, encoding 490 amino acids, and conservative between different species. The Arih2 gene was transcribed in various tissues at different developmental stages, and its transcriptional activities varied significantly between multiple tissues. With the development of chicken, Arih2 gene was basically up-regulated in heart, liver, kidney, skeletal muscle and glandular stomach, but fluctuated significantly in large intestine. In immune response, the transcriptional activities of Arih2 gene exhibited significant changes in the bursa, thymus and blood (P<0.05). The results showed that Arih2 might be a multifunctional gene involved in tissue development and immune response in chicken, and have a potential possible application as diagnostic marker for identifying immune response.