Abstract
Core cell cycle regulators, including cyclin-dependent kinases (CDKs), cyclins, and cyclin-dependent kinase inhibitors (CKIs), are known for their well-characterized roles in cell division. Several recent studies have shed light on the roles of these proteins in immune modulation. The development and activation of cells in the immune system take place not only during embryonic development but throughout the life of a multicellular organism. Cell cycle regulators are involved in the development of immune cells, partly as the machinery controlling the expansion and differentiation of the populations of immune cells. In addition, these proteins serve non-cell cycle functions. In this review, we summarize the emerging roles of cell cycle regulators in modulating functions of the immune system and discuss how they may be exploited as therapeutic targets.
Highlights
Multicellular organisms develop and maintain tissue homeostasis through cell division
Some of these functions may be related to cell division
The immunomodulatory functions of cell cycle regulators are unique among the non-cell cycle functions
Summary
Multicellular organisms develop and maintain tissue homeostasis through cell division. Cell division is governed by a group of core proteins called cyclin-dependent kinases (CDKs), cyclins, and cyclin-dependent kinase inhibitors (CKIs), which are negative regulators of CDKs. Growth factors induce the expression of D cyclins (cyclins D1, D2, and D3), which are regarded as molecular links between the cell environment and the core cell cycle machinery. D cyclins bind to CDK4 or CDK6 and phosphorylate the pocket proteins pRB, p107, and p130, which bind and regulate E2F transcription factors during the G1 phase of the cell cycle. During late G1, E cyclins (cyclins E1 and E2) become upregulated and activate CDK2, resulting in phosphorylation of various cell cycle-related proteins. More detailed information on these proteins can be found in recent articles (Malumbres, 2014; Hydbring et al, 2016)
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