The CDKN1C gene provides instructions for creating a protein that regulates cell growth and development. This protein helps control how and when cells divide.
The Role of CDKN1C in the Body
The CDKN1C gene produces a protein often referred to as p57KIP2, which acts as a cyclin-dependent kinase inhibitor (CDKI). This protein functions by binding to and inhibiting cyclin-dependent kinases (CDKs), which are enzymes that drive the cell cycle forward. By inhibiting CDKs, CDKN1C helps to halt cell division, particularly at the G1 phase, preventing cells from growing and dividing too rapidly. This regulatory action is important for controlled cell proliferation and differentiation during development.
CDKN1C is also an imprinted gene, meaning its activity depends on which parent it was inherited from. The copy of the gene inherited from the mother is typically more active than the paternal copy in most tissues. This parent-specific expression is regulated by genomic imprinting, involving chemical modifications like methylation on a nearby DNA region. The proper functioning of CDKN1C helps regulate overall growth, including preventing excessive fetal growth before birth.
When CDKN1C Doesn’t Work as Expected
When the function of the CDKN1C gene is altered, it can lead to various health conditions, primarily affecting growth. A significant example is Beckwith-Wiedemann Syndrome (BWS), an overgrowth disorder characterized by features like increased size at birth, a large tongue (macroglossia), and abdominal wall defects. In BWS, altered CDKN1C function often results from epigenetic changes, such as reduced methylation of the maternal allele in the 11p15.5 chromosomal region. This reduction in CDKN1C activity removes its normal restraint on cell growth, contributing to the overgrowth.
Mutations within the CDKN1C gene can also cause BWS, accounting for about 8% of cases, including both sporadic and familial forms. These mutations can lead to a non-functional or improperly functioning CDKN1C protein, disrupting the balance between “grow” and “don’t grow” signals in cells. CDKN1C is also recognized as a tumor suppressor gene, helping prevent tumor formation. When its function is compromised, either through mutations or epigenetic changes, it can contribute to the development of various cancers, including embryonal tumors and certain adult cancers, such as breast cancer.
Diagnosing and Understanding CDKN1C-Related Conditions
Identifying conditions linked to CDKN1C dysfunction typically involves a combination of clinical evaluation and genetic testing. Clinicians observe specific signs and symptoms, such as the characteristic overgrowth and physical features associated with Beckwith-Wiedemann Syndrome (BWS). Genetic testing is then used to confirm a diagnosis and determine the underlying molecular cause.
Genetic tests for CDKN1C-related conditions often include methylation analysis of the 11p15.5 chromosomal region to detect epigenetic changes that impact CDKN1C activity. Direct sequencing of the CDKN1C gene is also performed to identify specific mutations that can alter protein function. These tests help determine the specific genetic or epigenetic anomaly, which is important for understanding the condition’s inheritance patterns and for genetic counseling.
Current Research and Therapeutic Insights
Ongoing research continues to deepen the understanding of CDKN1C’s molecular mechanisms. Scientists are investigating how subtle changes in gene expression or protein function contribute to disease development. These studies aim to uncover how CDKN1C regulates cell growth and differentiation pathways.
Efforts also focus on developing new diagnostic tools for CDKN1C-related alterations. Research explores CDKN1C as a prognostic biomarker in certain cancers to predict patient outcomes and guide treatment. Therapeutic strategies are also being explored, particularly in cancer research, to potentially restore tumor suppressor function or target pathways where CDKN1C dysregulation occurs. This includes investigating compounds that may influence CDKN1C and related pathways to affect cancer cells.