Cold Spring Harbor, N.Y. Some cellular proteins have multiple, and occasionally opposing, functions. Professor Adrian Krainer [link: Faculty profile] and colleagues at Cold Spring Harbor Laboratory demonstrate in a paper published online today in Molecular Cell [link: to paper via doi #] that the oncogenic protein SRSF1 can also trigger a stop in cell growth and prevent cancerous proliferation by stabilizing p53, the powerful tumor-suppressor protein.
SRSF1 is a protein with many jobs. It was first described as necessary for the process in which mRNA, the messenger molecule transcribed from DNA to act as the template by which proteins are made, is cut and pasted into different genetic arrangements. This is known as "splicing." It has also been shown to be involved in many other processes relating to RNA metabolism.
Krainer's group has also previously implicated SRSF1 in cancer. They showed that when overexpressed in immortal fibroblast or epithelial cells it drives transformation and causes them to grow in a cancerous manner known as oncogenic proliferation. It is also expressed at markedly high levels in various tumors, including lung and breast cancer.
SRSF1 has also been shown to shuttle in and out of the cell's nucleus. This suggests it is involved in various processes that occur in either nuclear or cytoplasmic compartments. To investigate the diverse roles of SRSF1, a former graduate student in the Krainer lab, Oliver Fregoso (now a postdoc at the Fred Hutchinson Cancer Research Center in Seattle) initiated a study to look for other proteins that SRSF1 interacts with.
While he got lots of "hits," the key to the puzzle was to separate the signal from noise, i.e., to determine what was a real interaction and what wasn't. Further investigation revealed that a protein called RPL5 interacted specifically with SRSF1. RPL5 forms part of the ribosome, a large complex of RNAs and proteins responsible for the translation
|Contact: Edward Brydon Ph.D.|
Cold Spring Harbor Laboratory