Distinct functions of HTLV-1 Tax1 from HTLV-2 Tax2 contribute key roles to viral pathogenesis

While the human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), to date, its close relative HTLV-2 is not associated with ATL or other types of malignancies. Accumulating evidence shows that HTLV-1 Tax1 and HTLV-2 Tax2 have many shared activities, but the two proteins have a limited number of significantly distinct activities, and these distinctions appear to play key roles in HTLV-1 specific pathogenesis. In this review, we summarize the functions of Tax1 associated with cell survival, cell proliferation, persistent infection as well as pathogenesis. We emphasize special attention to distinctions between Tax1 and Tax2

Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones

The insulin/insulin-like growth factor signalling axis is an evolutionary ancient and highly conserved hormonal system involved in the regulation of metabolism, growth and lifespan in animals. Human insulin is stored in the pancreas, while insulin-like growth factor-1 (IGF-1) is maintained in blood in complexes with IGF-binding proteins (IGFBP1–6). Insect insulin-like polypeptide binding proteins (IBPs) have been considered as IGFBP-like structural and functional homologues. Here, we report structures of the Drosophila IBP Imp-L2 in its free form and bound to Drosophila insulin-like peptide 5 and human IGF-1. Imp-L2 contains two immunoglobulin-like fold domains and its architecture is unrelated to human IGFBPs, suggesting a distinct strategy for bioavailability regulation of insulin-like hormones. Similar hormone binding modes may exist in other insect vectors, as the IBP sequences are highly conserved. Therefore, these findings may open research routes towards a rational interference of transmission of diseases such as malaria, dengue and yellow fevers

The scribble-Dlg-Lgl module in cell polarity regulation

Although the Scribble polarity module has long been known as a key regulator of apicobasal polarity, it is only recently that its broader role in the control of near all polarity states and transitions is being appreciated. Here we review the Scribble module in the regulation of cell polarity and other cellular functions at the molecular and cellular level. The more recent detailed analysis of multiple vertebrate models for each of its component homologues, Scribble, Dlg and Lgl, has revealed specific but also common roles for individual homologues in a variety of developmental contexts. In addition, emerging data has also implicated the Scribble polarity module in human developmental syndromes and the etiology of human cancer, highlighting a need for a better understanding of this polarity module for therapeutic purposes. Unlocking the temporal and spatial coordination of the myriad interactions that these signaling scaffolds regulate is a major challenge for the field and will be key to resolve the function of Scribble, Dlg, and Lgl in the control of cell polarity and tissue architecture