On page 1193, Sakaguchi et al. identify S100C as a protein that is downregulated in immortalized cells. But their final conclusion has far greater significance: S100C may be the elusive contact-inhibition signal.
In semiconfluent cells S100C is cytoplasmic, interacts with actin filaments and, when overexpressed, induces the formation of actin-rich membrane protrusions. Expression levels of S100C increase with approaching confluence. In confluent normal cells, but not in confluent immortalized cells, threonine 10 of S100C is phosphorylated, inducing translocation of S100C into the nucleus.
Inhibition of S100C with injected antibodies causes confluent quiescent cells to resume DNA synthesis. The opposite treatment brings the opposite result: forced nuclear entry of S100C in HeLa cells (achieved with a nuclear localization sequence) turns on the cyclin-dependent kinase (cdk) inhibitors p16 and p21 and inhibits DNA synthesis. Thus, S100C is an excellent candidate for...
