SUZ12 (Suppressor of Zeste 12) is a gene found within human cells that codes for a protein regulating cellular processes. This protein is a component of a larger complex that controls how genes are expressed without altering the underlying DNA sequence. Its presence is widespread across various tissues and cell types, underscoring its broad involvement in maintaining cellular health and function.
Normal Function of SUZ12
SUZ12 functions as a core component of the Polycomb Repressive Complex 2 (PRC2), a multiprotein complex that plays a significant role in gene regulation. Within PRC2, SUZ12 contributes to the complex’s ability to silence specific genes through a process known as epigenetic silencing. This silencing occurs by adding methyl groups to lysine 27 of histone H3 (H3K27me3), a modification that compacts chromatin and makes genes inaccessible for transcription.
The PRC2 complex, with SUZ12 as a stabilizing element, ensures that certain genes remain inactive in specific cell types, which is important for maintaining cell identity. For example, a muscle cell needs its muscle-specific genes active, while genes for nerve cells should be silenced. This precise gene silencing helps to prevent unintended gene activation, thereby ensuring proper cellular function and stability. This mechanism of gene regulation is distinct from genetic mutations, as it involves changes to how DNA is packaged rather than changes to the DNA sequence itself.
SUZ12’s Role in Development
The precise control over gene expression by SUZ12 is important during embryonic development and cell differentiation. As part of the PRC2 complex, SUZ12 guides cells to develop into their correct types, such as a skin cell or a nerve cell, and ensures the proper formation of organs. Without this precise control, cells might fail to specialize correctly or might develop into unintended cell types, leading to developmental abnormalities.
SUZ12’s involvement extends to stem cell biology, where it helps maintain pluripotency, the ability of stem cells to differentiate into various cell types. Inactivation of SUZ12 in mouse embryos, for instance, leads to severe developmental defects and early lethality, indicating its role in proper embryonic progression. The loss of SUZ12 also results in a global reduction of H3K27me3, which impacts the expression of genes that are necessary for early embryogenesis.
When SUZ12 Goes Wrong: Disease Connections
When SUZ12’s normal function is disrupted, it can contribute to the development and progression of various diseases, with a strong link to cancer. Both an excess of SUZ12 activity (overexpression) and changes within the SUZ12 gene (mutations) can lead to uncontrolled cell growth and tumor formation. SUZ12 can act as either an oncogene (promoting cancer) or a tumor suppressor (preventing cancer), depending on the specific cancer type and the nature of the alteration.
Overexpression of SUZ12 has been observed in several solid cancers, including colorectal, ovarian, and non-small cell lung cancer, where it is often associated with aggressive disease features and poorer patient outcomes. In lung cancer, SUZ12’s elevated expression has been found to promote tumor cell growth, migration, and invasion. Conversely, in certain sarcomas, such as malignant peripheral nerve sheath tumors (MPNST), inactivating mutations or loss of SUZ12 function contribute to tumor initiation and progression. This dual role highlights the intricate balance required for SUZ12’s healthy function and how its dysregulation can drive different cancerous pathways.
Targeting SUZ12 for Treatment
Understanding SUZ12’s involvement in disease, especially in cancer, has opened new avenues for therapeutic strategies. Researchers are exploring ways to modulate SUZ12 activity, often by targeting the PRC2 complex. Inhibiting PRC2 activity, for example, has shown promise in increasing the sensitivity of certain cancer cells to existing treatments, such as TRAIL-mediated apoptosis in colon cancer.
This approach often involves small molecule inhibitors that specifically block the enzymatic activity of PRC2, or by reducing SUZ12 protein levels. While directly targeting SUZ12 itself is an active area of research, the focus is often on its role within PRC2, given that SUZ12 is important for the complex’s overall stability and function. These investigations aim to exploit the vulnerabilities created by SUZ12 dysregulation in cancer cells, offering a pathway toward more targeted and effective treatments.