Liongue Clifford, Ward Alister C
School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC 3216, Australia.
Int J Mol Sci. 2025 Apr 8;26(8):3498. doi: 10.3390/ijms26083498.
Cytokine receptor-like factor 3 (CRLF3) has an extended evolutionary history, which has been conserved across metazoan species. It consists of several structural elements, notably including a fibronectin type 3 (FBNIII) domain containing a WSXWS motif that is synonymous with so-called class I cytokine receptors present throughout bilaterial species, and a proposed spl1 and ryanodine receptor (SPRY) domain that represents a widespread protein-protein interaction module. The function of CRLF3 has remained enigmatic, but several recent investigations have revealed critical insights into its biological roles. These studies suggest that CRLF3 principally functions in neural and hematopoietic cells, where it plays critical and diverse roles in the development and function of specific cell populations. Disruption of CRLF3 has also been associated with several human diseases, mainly associated with these same lineages but also including malignancy. The mechanisms by which CRLF3 exerts these diverse effects remain uncertain, although a number of potential options have emerged.
细胞因子受体样因子3（CRLF3）具有悠久的进化历史，在多细胞动物物种中保守存在。它由几个结构元件组成，特别是包含一个纤连蛋白3型（FBNIII）结构域，该结构域含有一个WSXWS基序，这与整个双侧物种中存在的所谓I类细胞因子受体同义，以及一个推测的spl1和兰尼碱受体（SPRY）结构域，该结构域代表一种广泛存在的蛋白质-蛋白质相互作用模块。CRLF3的功能一直成谜，但最近的几项研究揭示了对其生物学作用的关键见解。这些研究表明，CRLF3主要在神经细胞和造血细胞中发挥作用，在特定细胞群体的发育和功能中起着关键且多样的作用。CRLF3的破坏也与多种人类疾病有关，主要与这些相同的细胞谱系有关，但也包括恶性肿瘤。尽管已经出现了一些潜在的机制，但CRLF3发挥这些多样作用的机制仍不确定。
