Cyclin-dependent kinase inhibitor 1C

Cyclin-dependent kinase inhibitor 1C (CDKN1C), also known as p57^Kip2, is a protein that in humans is encoded by the CDKN1C gene. This protein belongs to the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors and plays a critical role in cell cycle regulation. CDKN1C functions as a negative regulator of cell proliferation and has been implicated in the control of cell differentiation and apoptosis.

Function

CDKN1C is a potent cyclin-dependent kinase inhibitor that operates in the G1 phase of the cell cycle, blocking the transition from G1 to S phase by inhibiting the activity of cyclin-CDK2 or -CDK4 complexes. This inhibition is crucial for ensuring proper cell growth, differentiation, and development. The protein is particularly important in the regulation of placental development and has been shown to play a role in maintaining the pluripotency of embryonic stem cells.

Gene and Expression

The CDKN1C gene is located on the short (p) arm of chromosome 11 at position 15.5 (11p15.5), within a region implicated in several genetic disorders and cancers. The gene is imprinted, meaning that it is expressed in a parent-of-origin-specific manner; typically, only the maternal allele is active while the paternal allele is silenced. This imprinting status makes CDKN1C a key player in the development of Beckwith-Wiedemann syndrome, a growth disorder associated with an increased risk of childhood cancers.

Clinical Significance

Alterations in the expression or function of CDKN1C are associated with various human diseases. Loss of function mutations or reduced expression of the CDKN1C gene has been linked to an increased risk of developing certain cancers, including breast cancer, lung cancer, and prostate cancer. Conversely, overexpression of CDKN1C has been observed in some conditions associated with growth restriction, such as Silver-Russell syndrome.

In addition to its role in cancer, mutations in the CDKN1C gene can lead to developmental disorders. The most notable of these is Beckwith-Wiedemann syndrome (BWS), a condition characterized by overgrowth and an increased risk of pediatric tumors. CDKN1C mutations are one of the genetic alterations that can cause BWS, particularly those mutations that reduce the protein's inhibitory function on cell proliferation.

Therapeutic Potential

Given its pivotal role in cell cycle regulation and disease, CDKN1C is considered a potential target for therapeutic intervention. Strategies to modulate its activity are being explored in the context of cancer treatment, aiming to restore normal cell cycle control in cancer cells by either inhibiting or enhancing CDKN1C function, depending on the cancer type and the underlying mechanism of disease.

See Also

• Cyclin-dependent kinase inhibitor
• Cell cycle
• Beckwith-Wiedemann syndrome
• Imprinting (genetics)