AF4p12, a Human Homologue to the furry Gene of Drosophila, as a Novel MLL Fusion Partner

Abstract

More than 35 different partner genes with the mixed lineage leukemia (MLL) gene have been cloned from leukemia cells with translocations involving chromosome 11 band q23. In this study, we report on a novel fusion partner of the MLL gene, AF4p12, which we have identified as the human homologue to the furry gene of Drosophila. AF4p12, highly conserved in evolution, encodes a large protein of 3,105 amino acids. The expression of AF4p12 has been preferentially detected in colon, placenta, and brain tissues and in tumor cells of lymphoid origin. We show that the t(4;11)(p12;q23) translocation results in the creation of a chimeric RNA encoding a putative fusion protein containing 1,362 amino acids from the NH 2 -terminal part of MLL and 712 amino acids from the COOH-terminal part of AF4p12. FLT3 and HOXA9 genes are overexpressed in this leukemia. We found that the COOH-terminal part of AF4p12 fused to MLL contains a leucine zipper motif and exhibits transcriptional activation properties when fused to Gal4 DNA-binding domains in transient transfection assays. The AF4p12 fragment fused to MLL may contribute to the oncogenic activation of MLL, possibly through specific recruitment of the transcriptional machinery. (Cancer Res 2005; 65(15): 6521-5)

Xenopus furry contributes to release of microRNA gene silencing

“…The blot results suggest that Xfurry localizes to nuclei via the LZ structure and that the localization of Xfurry depends on the localization of partner proteins interacting via its FD and LZ domains. This evidence, together with the evidence that human furry has transcriptional properties in acute myeloid leukemia patients (8), supports the hypothesis that Xfurry enters the nucleus and functionally resembles a transcription factor. However, the LZ domain alone had no effect on axis formation (Table S1), indicating that another domain, the FD, is necessary for axis formation.…”

“…However, Furry also is found in the nuclei of salivary gland and fat body cells in the fly, suggesting an additional function in gene regulation (2). Human furry also has shown transcriptional regulatory properties in acute myeloid leukemia patients (8). Together, these observations suggest that furry functions in the nucleus, possibly in transcriptional regulation, and also highlight that much is unknown about the function of furry, especially in vertebrate embryogenesis.…”

Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome

“…Although MLL-FRYL ultimately proved a harbinger to secondary MDS, different gene expression patterns, including low MEIS1 expression and the long latency and protracted course without clinical disease, indicate that MLL-FRYL is unlike typical MLL translocations. The same partner gene called AF4p12 was identified in a case of secondary acute lymphoblastic leukemia (ALL), 23 during the time when the patient we describe was being observed, indicating that FRYL is a recurrent partner gene of MLL.…”

Temporal Profile of Brain Gene Expression After Prey Catching Conditioning in an Anuran Amphibian

“…At 2 h, genes like catenin beta-2 (ctnnb2), serine/threonine-protein kinase ULK1 (ulk1), ephrin type-A receptor 8 (epha8), and gamma-aminobutyric acid receptor-associated protein (gabarap), associated with the generation of new neurites (Okazaki et al, 2000;Coyle et al, 2002;Gu et al, 2005;Lin et al, 2009), are highly suppressed. At 4 h the same pattern is observed, with suppression of genes like catenin alpha-2 (ctnna2; Schaffer et al, 2018), clathrin coat assembly protein AP180 (snap91; Bushlin et al, 2008), and protein furry homolog-like (fryl; Hayette et al, 2005). This contrasts with the late expression peak of neurite development genes like contactin-associated proteinlike 2 (cntnap2; Poliak et al, 1999), brain-specific angiogenesis inhibitor 1-associated protein 2 (baiap2; Kang et al, 2016), and protein furry homolog (fry; Hayette et al, 2005) at 24 h. These neuron projection development (GO:0031175) genes are also cytoskeletal modification genes.…”