The Role of SPOP During Development / 中国生物化学与分子生物学报

Aberrant expression or mutation of many genes that are essential for embryonic development, are closely associated with human diseases, one of which is SPOP (speckle type BTB/POZ protein). SPOP is an E3 ubiquitin ligase adaptor protein and mainly composed of MATH, BTB and BACK domains, which plays distinct roles to fulfill the proper function of SPOP. SPOP usually targets its substrates for degradation via the ubiquitin-proteasome pathway. More than thirty substrates of SPOP have been identified by far, most of which are associated with tumorigenesis of prostate, endometrial and kidney cancers. SPOP also plays an important role during development. Genomic loss or mutation of SPOP locus leads to postnatal lethality in mice, while de novo variants in SPOP cause neurodevelopmental disorders in children. Similarly, SPOP regulates a variety of developmental processes via targeting its substrates for degradation, including Gli2/3, PDX1, NANOG and SENP7 which are involved in neural, skeletal and pancreatic development as well as senescence. In addition, recent studies have revealed that SPOP co-localizes with its substrates into membraneless organelles such as nuclear speckles, and promotes ubiquitination and degradation of its substrates. Oligomerization of SPOP and liquid-liquid phase separation (LLPS) triggered by multivalent interactions between SPOP and substrates play a pivotal role in this process. BTB or BACK mutants, which are defective in SPOP oligomerization, are also defective in driving LLPS of SPOP and recruiting SPOP into membraneless organelles. In this review, we summarized and discussed the recent progress on the essential role of SPOP during development.

Directed differentiation embryonic stem cells into the chondrocyte / 中国医学科学院学报

Cartilage is a tough, elastic, and fibrous connective tissue, composed of chondrocyte and extracellular matrix (ECM) structural entity. Because of the poor self-regeneration capabilities of chondrocytes, cell transplantation is necessanry once the cartilage is damaged. Traditionally autologous chondrocytes implantation is applied at the damage site, which has many problems such as the losing of its primary characteristics. A well-defined and efficient protocol to direct the differentiation of embryonic stem cells into the chondrocyte will provide a novel choice for cartilage repair. This article reviews some major progresses in this field.