UC San Francisco researchers may have identified the way in which a protein that regulates genes involved in sexual differentiation, reproductive development and stress is, itself, activated.
If verified, the finding would signify a major breakthrough in understanding the modulation of a key regulator of the genes involved in such endocrine activities as the determination of sex, the development of sex organs and the way the body reacts to stress.
The finding could also, perhaps, be applied more generally, possibly explaining why some hormonally regulated cancers, such as of the breast and prostate, at times become resistant to anti-hormone therapies. For it suggests a possible alternative mechanism of action on these nuclear receptors in some cancer cells.
The finding, reported in the current issue of Molecular Cell, confirms what researchers have long suspected but been unable to prove - that the protein, a nuclear receptor known as steroidogenic factor 1, is regulated not by the "small molecule" hormones that regulate all other known nuclear receptors, but by a signaling cascade that culminates in phosphorylation, the addition of a phosphorous molecule to the receptor.
Nuclear receptors are a sophisticated brand of cellular proteins located inside the nucleus, where they receive signals and interact with other proteins to initiate changes in gene activity. The small-molecule hormones, or "ligands," that regulate most of these nuclear receptors sweep into a cell's nucleus from far-flung cells and latch on to their respective receptor, prompting it to bind with nearby molecular "co-factors." Together, the receptor and its co-factors bring about the change in a given gene's behavior.
The molecule, or ligand, that signals the SF-1 nuclear receptor to prompt a
change in gene activity has been elusive, however, leading to its designation as
an "orphan" receptor, and leaving researchers suspicious that some signal other
than a small-molecule h
'"/>
Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
26-Apr-1999