The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into new proteins, which is essential for the normal functioning and survival of cells. Mutations in the TCOF1, POLR1C, or POLR1D gene reduce the production of rRNA. Researchers speculate that a decrease in the amount of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. The abnormal cell death could lead to the specific problems with facial development found in TCS. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.
A study showed that oncogenic transformation by ras and fos requires Jun N-terminal phosphorylation at Serine 63 and 73 by the Jun N- terminal kinases (JNK). In this study, the induced skin tumor and osteosarcoma showed impaired development in mice with a mutant Jun incapable of N-terminal phosphorylation.  Also, in a mouse model of intestinal cancer, genetic abrogation of Jun N-terminal phosphorylation or gut-specific c-jun inactivation attenuated cancer development and prolonged lifespan.  Therefore, targeting the N-terminal phosphorylation of Jun (or the JNK signaling pathway) can be a potential strategy for inhibiting tumor growth.
Born in Athens, Greece, Dr. Sadis Matalon came to the United States in 1966 as an undergraduate Fulbright Scholar and subsequently received a Bachelor of Arts in Physics from Macalester College, cum laude with Special Departmental Honors (1970), followed by a Master of Science in Physics from the University of Minnesota (1973). He continued with a . in Physiology (1975) under the mentorship of . Wangensteen and entitled his dissertation “Water and Non-electrolyte Solute Transport across the Pulmonary Capillaries in Newborn Rabbits.” Read more