Institute of Molecular Biology and Pathology (IBPM), Consiglio Nazionale delle Ricerche (CNR), c/o Sapienza University, Rome, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Biochim Biophys Acta Mol Cell Res. 2023 Jun;1870(5):119465. doi: 10.1016/j.bbamcr.2023.119465. Epub 2023 Mar 20.
HIPK2 is an evolutionary conserved serine/threonine kinase with multifunctional roles in stress response, embryonic development and pathological conditions, such as cancer and fibrosis. The heterogeneity of its interactors and targets makes HIPK2 activity strongly dependent on the cellular context, and allows it to modulate multiple signaling pathways, ultimately regulating cell fate and proliferation. HIPK2 is highly expressed in the central and peripheral nervous systems, and its genetic ablation causes neurological defects in mice. Moreover, HIPK2 is involved in processes, such as endoplasmic reticulum stress response and protein aggregate accumulation, and pathways, including TGF-β and BMP signaling, that are crucial in the pathogenesis of neurological disorders. Here, we review the data about the role of HIPK2 in neuronal development, survival, and homeostasis, highlighting the implications in the pathogenesis of neurological disorders, and pointing out HIPK2 potentiality as therapeutic target and diagnostic or prognostic marker.
HIPK2 是一种进化上保守的丝氨酸/苏氨酸激酶，在应激反应、胚胎发育和病理状况（如癌症和纤维化）中具有多种功能。其相互作用物和靶标的异质性使 HIPK2 的活性强烈依赖于细胞环境，并使其能够调节多种信号通路，最终调节细胞命运和增殖。HIPK2 在中枢和外周神经系统中高度表达，其基因缺失会导致小鼠的神经缺陷。此外，HIPK2 参与内质网应激反应和蛋白质聚集积累等过程，以及 TGF-β和 BMP 信号等通路，这些过程和通路在神经疾病的发病机制中至关重要。在这里，我们回顾了 HIPK2 在神经元发育、存活和稳态中的作用的数据，强调了其在神经疾病发病机制中的意义，并指出了 HIPK2 作为治疗靶点和诊断或预后标志物的潜力。
