Department of Biochemistry, Centre for Biomolecular Interactions Bremen (CBIB), University of Bremen, Germany.
FEBS J. 2012 Mar;279(5):737-51. doi: 10.1111/j.1742-4658.2011.08464.x. Epub 2012 Jan 12.
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.
肝癌衍生生长因子相关蛋白 2（HRP-2）属于一个包含另外五个成员的家族：肝癌衍生生长因子（HDGF）；晶状体上皮衍生生长因子；以及 HDGF 相关蛋白-1、-3 和-4。关于 HRP-2 的功能，我们知之甚少。本研究首次显示 HRP 家族不同成员（HDGF 和 HRP-2）之间的异源二聚体形成。此外，我们发现了 HRP-2 mRNA 的一个以前未知的剪接变体，该变体编码在其 hath 区域缺失 53 个氨基酸的蛋白质。这种 HRP-2 同种型 c 与加工形式的 HDGF 优先相互作用，可能是因为 HRP-2 的α螺旋缺失。此外，与 HRP-2 的其他同种型不同，同种型 c 与染色质结合类似于其最密切相关的家族成员晶状体上皮衍生生长因子，这可能对其在 HIV 整合中的功能有潜在影响。有趣的是，只有新的 HRP-2 同种型 c 和加工形式的 HDGF 从浓缩的有丝分裂中期染色质中被置换。总之，这些观察结果为理解 HDGF 和相关蛋白的生物学功能提供了新的视角。
