Interaction of HRP‐2 isoforms with HDGF. Chromatin binding of a specific heteromer

Hepatoma‐derived growth‐factor‐related protein 2 (HRP‐2) belongs to a family with five additional members: hepatoma‐derived growth factor (HDGF); lens epithelium‐derived growth factor; and the HDGF‐related proteins ‐1, ‐3 and ‐4. Very little is known regarding the function of HRP‐2 in particular. This study shows for the first time heteromer formation of different members of the HRP family; HDGF and HRP‐2. In addition, we discovered a previously unknown splice variant of HRP‐2 mRNA encoding for a protein with a 53‐amino acid deletion in its hath region. This HRP‐2 isoform c interacts preferentially with a processed form of HDGF probably because of the loss of an α helix of HRP‐2. Furthermore, in contrast to other isoforms of HRP‐2, isoform c binds to chromatin similar to its most closely related family member lens epithelium‐derived growth factor with potential consequences regarding its function in HIV integration. Interestingly, only the new HRP‐2 isoform c and a processed form of HDGF are displaced from condensed mitotic metaphase chromatin. In conclusion, these observations provide a new perspective for understanding the biological functions of HDGF and related proteins. Structured digital • HRP2 a and Hdgf physically interact by bimolecular fluorescence complementation (View interaction) • HRP2 a and Hdgf colocalize by fluorescence microscopy (View interaction) • HRP2 b physically interacts with Hdgf by pull down (View Interaction: 1, 2) • Hdgf and HRP2 c physically interact by bimolecular fluorescence complementation (View interaction) • Hdgf and HRP2 b colocalize by fluorescence microscopy (View interaction) • HRP2 a physically interacts with Hdgf by pull down (View Interaction: 1, 2) • Hdgf and HRP2 b physically interact by bimolecular fluorescence complementation (View interaction) • HRP2 c physically interacts with Hdgf by pull down (View Interaction: 1, 2) • Hdgf and HRP2 c colocalize by fluorescence microscopy (View interaction) This study shows for the first time heteromer formation of different members of the hepatoma‐derived growth‐factor‐related protein 2 (HRP) family ‐ HDGF and HRP‐2. Additionally, we discovered a previously unknown splice variant of HRP‐2 mRNA encoding for a protein with a 53 amino acid deletion in its hath region. This HRP‐2 isoform c interacts preferentially with a processed form of HDGF.