CHEK1

CHEK1

CHEK1 (Checkpoint kinase 1) is a serine/threonine-specific protein kinase that plays a critical role in the cell cycle checkpoint control and DNA damage response. It is encoded by the CHEK1 gene in humans.

Function

CHEK1 is a key regulator of the cell cycle, particularly in the response to DNA damage. It is activated in response to DNA replication stress and double-strand breaks, primarily through the ATR (Ataxia Telangiectasia and Rad3-related protein) signaling pathway. Once activated, CHEK1 phosphorylates a variety of substrates involved in cell cycle arrest, DNA repair, and apoptosis.

CHEK1's primary function is to delay cell cycle progression in the S and G2 phases, allowing time for DNA repair before mitosis. It achieves this by phosphorylating and inhibiting CDC25 phosphatases, which are responsible for activating cyclin-dependent kinases (CDKs) that drive cell cycle progression.

Clinical Significance

CHEK1 is a potential target for cancer therapy due to its role in maintaining genomic stability. Inhibitors of CHEK1 are being investigated as potential treatments for cancer, particularly in tumors with defective p53, where the reliance on CHEK1 for cell cycle arrest is increased.

Mutations or dysregulation of CHEK1 can lead to genomic instability and contribute to tumorigenesis. Overexpression of CHEK1 has been observed in various cancers, including breast, lung, and colorectal cancers.

Interactions

CHEK1 interacts with several proteins involved in the DNA damage response and cell cycle regulation, including:

• ATR
• CDC25A
• CDC25C
• Claspin
• BRCA1

Research

Ongoing research is focused on understanding the precise mechanisms of CHEK1 activation and its role in cancer. Studies are also exploring the development of CHEK1 inhibitors as therapeutic agents, either alone or in combination with other treatments such as chemotherapy and radiation.

Also see

• Cell cycle
• DNA damage response
• Checkpoint kinase 2 (CHEK2)
• ATR (protein)
• BRCA1