AsianScientist (May 27, 2014)  – Scientists have uncovered the functions of alternative forms of the tumor suppressor PTEN, challenging the central dogma of biology which states that each gene only codes for one functional protein. This research has been published in the journal Cell Metabolism .

PTEN is a powerful tumor suppressor that is frequently mutated or switched off in many human cancers. Conventional wisdom holds that the PTEN gene, like most other genes, should produce only a single protein form.

However, a team of researchers at the Peking University Health Science Center and Weill Cornell Medical College 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.

Although PTENα appears to be just an elongated form of PTEN, it is different from PTEN in critical ways, says co-senior author Dr. Shen Wen Hong from Weill Cornell’s Department of Radiation Oncology. While translation of genes usually begins at what is known as an AUG start codon, PTENα translation starts at a different codon on the PTEN gene, CUG. 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 has different functions and localization patterns than PTEN. 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. 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, Shen says.

The article can be found at: Liang et al. (2014) PTENα, a PTEN Isoform Translated through Alternative Initiation, Regulates Mitochondrial Function and Energy Metabolism.

Source: Weill Cornell Medical College

Edited by: Arthars