CDK2 (Phospho-Thr160) ELISA Kit

Precise execution of the cell division cycle is vital for all organisms. The Cyclin dependent kinases (CDKs) are the main cell cycle drivers, however, their activities must be precisely fine-tuned to ensure orderly cell cycle progression. A major regulatory axis is guarded by WEE1 kinase, which directly phosphorylates and inhibits CDK1 and CDK2. The role of WEE1 in the G2/M cell-cycle phase has been thoroughly investigated, and it is a focal point of multiple clinical trials targeting a variety of cancers in combination with DNA-damaging chemotherapeutic agents. However, the emerging role of WEE1 in S phase has so far largely been neglected. Here, we review how WEE1 regulates cell-cycle progression highlighting the importance of this kinase for proper S phase. We discuss how its function is modulated throughout different cell-cycle stages and provide an overview of how WEE1 levels are regulated. Furthermore, we outline recent clinical trials targeting WEE1 and elaborate on the mechanisms behind the anticancer efficacy of WEE1 inhibition. Finally, we consider novel biomarkers that may benefit WEE1-inhibition approaches in the clinic.

As the follicle develops, the thickening of the granulosa compartment leads to progressively deficient supply of oxygen in granulosa cells (GCs) due to the growing distances from the follicular vessels. These conditions are believed to cause hypoxia in GCs during folliculogenesis. Upon hypoxic conditions, several types of mammalian cells have been reported to undergo cell cycle arrest. However, it remains unclear whether hypoxia exerts any impact on cell cycle progression of GCs. On the other hand, although the GCs may live in a hypoxic environment, their mitotic capability appears to be unaffected in growing follicles. It thus raises the question whether there are certain intraovarian factors that might overcome the inhibitory effects of hypoxia. The present study provides the first evidence suggesting that cobalt chloride (CoCl2)-mimicked hypoxia prevented G1-to-S cell cycle progression in porcine GCs. In addition, we demonstrated that the inhibitory effects of CoCl2 on GCs cell cycle are mediated through hypoxia-inducible factor-1 alpha/FOXO1/Cdkn1b pathway. Moreover, we identified insulin-like growth factor-I (IGF-I) as an intrafollicular factor required for cell cycle recovery by binding to IGF-I receptor in GCs suffering CoCl2 stimulation. Further investigations confirmed a role of IGF-I in preserving G1/S progression of CoCl2-treated GCs via activating the cyclin E/cyclin-dependent kinase2 complex through the phoshatidylinositol-3 kinase/protein kinase B (AKT)/FOXO1/Cdkn1b axis. Although the present findings were based on a hypoxia mimicking model by using CoCl2, our study might shed new light on the regulatory mechanism of GCs cell cycle upon hypoxic stimulation. Summary sentence The IGF-I/PI3K/AKT/FOXO1/Cdkn1b axis is essential for preserving G1/S progression in hypoxic porcine GCs by targeting cyclin E/CDK2.