The CDKN1B gene is associated with autosomal dominant multiple endocrine neoplasia (MEN), type 4. (MEN4)
At least eight mutations in the CDKN1B gene have been found to cause a relatively rare form of multiple endocrine neoplasia called type 4. Multiple endocrine neoplasia typically involves the development of tumors in two or more of the body's hormone-producing glands, called endocrine glands. These tumors can be noncancerous or cancerous. The most common endocrine glands affected in multiple endocrine neoplasia type 4 are the parathyroid glands and the pituitary gland, although additional endocrine glands and other organs can also be involved.
Hyperparathyroidism is the most common finding, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.
Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. Some mutations impair the protein's ability to interact with regulatory proteins, while others lead to the production of an unstable version of p27 that is quickly broken down. Still other mutations prevent p27 from moving from the cytoplasm into the nucleus. All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. Cells with a shortage of functional p27 can divide too quickly or in an uncontrolled way, forming a tumor. It is unclear why these tumors occur primarily in endocrine glands; studies suggest that certain endocrine cells may be particularly dependent on the p27 protein to control cell division.
The CDKN1B gene provides instructions for making a protein called p27. This protein is found in cells and tissues throughout the body. Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. It helps regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. Specifically, p27 normally blocks cells from entering the phase of the cell cycle when DNA is copied (replicated) in preparation for cell division. By blocking cell cycle progression, p27 prevents cells from dividing too quickly or at the wrong time. Based on this function, p27 is described as a tumor suppressor protein. Studies suggest that p27 is also involved in controlling cell differentiation, which is the process by which cells mature to carry out specific functions.