HORMONES AND CYTOKINES Alternative Protein Export Pathway - Brief Article

Applied Genetics News, April, 2000

Scientists at Ciblex Corp. (11025 Roselle St., San Diego, CA 92121; Tel: 619/546-7848, Fax: 619/546-7596, Website: www.ciblex.com) have identified a protein sequence that permits fibroblast growth factor 2 (FGF2) to exit cancer cells and stimulate blood vessel and tumor growth. This research, reported at the 91st American Association for Cancer Research meeting (San Francisco, CA), represents the first step towards characterizing a non-classical protein trafficking pathway. Ciblex scientists believe that blocking this protein export pathway offers a new approach to treating cancer and other diseases.

Proteins are normally transported out of a cell by virtue of having a specific amino acid sequence called a "leader peptide." The leader sequence acts as a signal for the protein to enter the classical "secretion" pathway, which routes proteins through cellular machinery called the Golgi apparatus and endoplasmic reticulum (ER) before being secreted outside the cell. Certain disease-causing proteins, such as FGF2, do not have this leader peptide sequence and are exported out of cells through an alternative, non-classical pathway that bypasses the Golgi and ER.

Ciblex scientists identified the unique region of the FGF2 protein sequence that is responsible for its alternative export out of U87-MG glioblastoma cells. The scientists systematically combined different portions of the protein sequences from FGF2 and a related protein called FGF1, which is not normally exported from U87-MG cells. By tracking the transport of each FGF2/FGF1 chimera, the specific export signaling sequence inherent to FGF2 was identified through its ability to promote the export of FGF1.

"We believe that our focus on the export pathway will allow intervention at the earliest and possibly most effective point--before a disease-causing protein leaves the cell and causes harm," says Gary Hooper, president and CEO.