Transcription Factors and Co-Factors

Transcription factors and their cofactors are proteins or protein complexes activated by events or substances at the cellular level. These stimuli include injury and toxins. ^{(iii.2, 10, 14, 21-26)}

Why Are Transcription Factors Activated?

Transcription factors are some of the body's first responders to an injury or harmful stressor. This makes them part of the immune system's normal, acute inflammatory response. Sometimes, however, they can be part of a disease-promoting process — such as when they activate oncogenes involved in cancer. ^{(iii.2, 10, 14, 22-26)}

Transcription Factor & Co-Factor Functions

Once activated, transcription factors and cofactors bind to and turn on genes located in specific regions on DNA strands in the cell nucleus. These genes provide instructions, or codes, for making specific proteins. ^{(iii.2, 10, 14, 21-26)}

Binding to these genes prompts transcription, which is the process of making the proteins from the instructions. The proteins produced can even include other transcription factors needed to activate different genes. ^{(iii.2, 10, 14, 21-26)}

When oncogenes are activated by transcription factors they also produce proteins. Many of these proteins are essential to health under normal circumstances. When induced by oncogenes, however, they promote tumor growth and metastasis. These include: ^{(iii.27, 28)}

• Inflammatory enzymes
• Growth factors
• Survival factors

Oncogenes can also stimulate overproduction of inflammatory cytokine proteins. All of these factors generate free radicals and overload the body’s antioxidant defenses. In addition, some proteins from oncogenes block tumor suppressor proteins. ^{(iii.27, 28)}

Effects of Turmeric Compounds on Transcription Factors and Co-Factors

The turmeric compound curcumin and its related compounds block a number of different transcription factors responsible for activating oncogenes and pro-inflammatory genes. Decades of research indicates that the turmeric compound curcumin is a potent inhibitor of NF-κB transcription factor family of proteins that are involved in many diseases. Curcumin protects cells and cell mitochondria from the damage caused by NF-κB's activity. ^{(iii.2, 10, 14, 22-26)}

On the other hand, turmeric compounds stimulate transcription factors that prompt genes to produce natural detoxifying antioxidants. Curcumin's antioxidant properties help quench excess free radicals produced in chronic inflammatory environments. ^{(iii.2, 10, 14, 22-29)}

Perhaps even more intriguing is curcumin's ability to stimulate or suppress the same transcription factor, depending on the type of cell. CREB transcription factors are a good illustration of curcumin's tissue and condition-specific behavior. In cancer cells, curcumin inhibits the CREB transcription factors associated with uncontrolled cell growth. However, in the brain it promotes CREB to maintain healthy neuron cells. ^{(iii.2, 10, 14, 22-29)}

Studies indicate that curcumin helps regulate expression of some cofactors, including transcription factors that can also act as cofactors. For example, by inhibiting its transcription factor cofactors, curcumin blocks the activation of the androgen-receptor (AR) transcription factor. This could be helpful in preventing or treating prostate cancer. ^{(iii.2, 10, 30, 31)}