Cell Cycle Inhibitor Proteins


 Cell Cycle Inhibitor Proteins Background

The majority of studies that have shown that cell cycle components are important to regulation of organogenesis focus on key elements of the G1 to S transition phase of the cell cycle. In order for cells to progress through this checkpoint, cyclin/cyclin dependent kinase complexes must hyper-phosphorylate Rb, deactivating its repressive activity. Proliferating cells are then transitioned into late G2 and into M phase where mitotic division ultimately expands the progenitor pool. In order for cells to undergo differentiation, this progressive movement through the cell cycle must be halted. A class of proteins called cyclin dependent kinase inhibitors (CDKIs) is responsible for binding to cyclin/cyclin dependent kinase complexes and preventing their phosphorylation activities. As these complexes are inhibited, cells exit the cell cycle and enter into a quiescent phase (G0). In this state, cells are poised to determine cell fate by reentering the cell cycle or undergoing differentiation. And cell cycle inhibitors play an important role in this process.

For example, CDKIs are one type of cell cycle inhibitors. CDKI regulation of differentiation has been shown to be a shared mechanism in tissues throughout the body. Yet, the role of CDKIs in pituitary development has only recently been explored. p27 expression has also been shown to prevent pituitary cell proliferation by repressing differentiated cell proliferation in the pituitary. Loss of p57 results in accumulation of proliferating progenitors and subsequent hyperplasia of the pituitary, while overexpression of p57 leads to pituitary hypoplasia. Furthermore, recent studies have shown that p57 expression is needed to promote cell cycle exit of proliferating pituitary progenitors in conjunction with p27. These studies highlight the importance of cell cycle inhibitors in controlling proliferation and differentiation of progenitors in the pituitary.