Pin1

Pin 1, or peptidyl-prolyl cis/trans isomerase (PPIase), isomerizes only phospho-Serine/Threonine-Proline motifs. The enzyme binds to a subset of proteins and thus plays a role as a post phosphorylation control in regulating protein function. Studies have shown that the deregulation of Pin1 may play a pivotal role in various diseases. Notably, the up-regulation of Pin1 may be implicated in certain cancers, and the down-regulation of Pin1 may be implicated in Alzheimer's disease.[1]

Discovery and characterization
The gene encoding Pin1 was identified in 1996 as a result of a genetic/biochemical screen for proteins involved in mitotic regulation. It was found to be essential for cell division in some organisms.

Activation of Pin1
Pin1 is dependent on the phosphorylation of its substrates. It is a small protein at 18 kDa and does not have a nuclear localiztation or export signal. Substrate interactions and a WW domain determine subcellular distribution. Expression is induced by growth signals from E2F transcription factors. Expression levels fluctuate in normal, but not in cancerous cells. Expression is often associated with cell proliferation. Postranslational modifications such as phosphorylation on Ser16 inhibit the ability of Pin1 to bind substrate, and this inhibitory process may be altered during oncogenisis. It is hypothesized, but not proven, that Pin1 might also be regulated by proteolytic pathways.

Biological function
Pin1's activity is thought to impact cell proliferation. Phosphorylation-specific isomerization is hypothesized to function as a timing mechanism that would allow the cell to control protein function.

[1]Lu, KP, Pinning Down Cell Signaling, Cancer, and Alzheimers Disease, Trends in Biochemical Sciences 2004, V29, N4; 200-208.