Syk-mediated Protein Degradation Serves as a Regulatory Mechanism in Terminal Erythropoiesis

Abstract

Terminal erythropoiesis is a complex process that requires stringent regulatory mechanisms to prevent aberrant changes that may lead to disastrous diseases. However, the regulatory mechanisms in terminal erythropoiesis is not fully understood yet. Here, we show that Syk participates in the protein degradation that controls cell cycle progression during terminal erythropoiesis.

Syk which is primarily expressed in hematopoietic lineage has well recognized roles in most of the hematopoietic lineage, but its role in terminal erythropoiesis remains unknown. In this study, we demonstrate that Syk regulates cell cycle during terminal erythropoiesis through proteolysis modulation. Syk deficiency leads to anemia at both fetal and adult stages. Extramedullary erythropoiesis takes place in the spleen of Syk knockout mice, resulting in splenomegaly as a consequence of ineffective erythropoiesis in the bone marrow. Impaired in vivo and ex vivo terminal erythropoiesis are reported at both fetal and adult stages after Syk loss. Afterall, knockout of Syk results in rapid Rb degradation that leads to abnormally upregulated E2F signaling and finally causes defective cell cycle exit during terminal erythropoiesis.

Altogether, our findings prove that Syk-mediated Rb stability is essential in maintaining proper progression of terminal erythropoiesis through protein degradation. This provides an insight to the importance of protein degradation as a regulatory mechanism in the terminal erythropoiesis.

Date of Award	3 Dec 2020
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Jiahai SHI (Supervisor)