PTEN has long been known to be a powerful tumor suppressor — it is frequently mutated or switched off in many human cancers. Conventional wisdom holds that PTEN produces only a single protein form; there is no PTEN family of proteins.
Now, however, in the April 24 issue of Cell Metabolism, a team of researchers at Weill Cornell Medical College and Peking University Health Science Center has discovered a sibling to PTEN that they call PTENα, a finding that calls into question what role this "family" of proteins is playing in cancer and perhaps other diseases. But that is just their first surprise.
Although PTENα appears to be just an elongated form of PTEN, it is different from PTEN in critical ways, says co-senior author Dr. Wen Hong Shen, an assistant professor of cell biology in Weill Cornell's Department of Radiation Oncology. She says that while translation of genes — the process that produces protein — usually begins at what is known as an AUG start codon, PTENα translation starts at a different codon on the PTEN gene. The researchers say this finding suggests an alternative way of making an additional protein from the same gene — an unusual process that may be going on in other genes and playing a role in cancer and other diseases.
The study also showed that PTENα resides and functions differently in the cell than PTEN does. While PTEN works in the cell's cytoplasm and nucleus, PTENα is not found in the nucleus. Instead, it functions mainly in the mitochondria, the cell's power plant. The scientists also found evidence that both proteins work together to regulate energy metabolism, helping to maintain routine cellular processes.
Cellular metabolism is an area of increasing interest for a wide variety of clinical fields, including cancer. Aberrant cellular metabolism has already been linked to disease. And since PTENα controls cellular metabolism and bears many mutations that cause its dysfunction, PTENα or the molecules it affects could be potential drug targets or biomarkers of disease, Dr. Shen says.
In order to be able to understand what goes wrong in diseases of metabolism, scientists need to understand how cellular metabolism normally functions and how it is regulated, she says, adding that this basic science study provides a promising foundation for future research to benefit patients.