p21 protein is a cyclin-dependent inhibitor.
The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This was a major discovery in the early 1990’s that revealed how cells stop dividing after being exposed to damaging agents such as radiation. In addition to growth arrest, p21 can mediate cellular senescence and one of the ways it was discovered was as a senescent cell-derived inhibitor
The p21 protein also is important in the stress response. p21 is the major transcriptional target of the tumor suppressor gene, p53; despite this, loss-of-function mutations in p21 (unlike p53) do not accumulate in cancer nor do they predispose to cancer incidence. Mice genetically engineered to lack p21 develop normally and are not susceptible to cancer at a higher rate than wild-type mice (unlike p53 knockout mice).
Mice that lack the p21 gene gain the ability to regenerate lost appendages.
Some select people show incredibly resistance to develop AIDS even after being infected by HIV. Scientists reported October 21 at a meeting of the Infectious Diseases Society of America that these people produce copious amounts of p21. Is there a relationship between the production of p21 and their ability to ward off AIDS even after being infected by HIV?
Researchers compared four groups of people — 14 who were HIV negative, 16 with HIV that had progressed, 10 with HIV who were undergoing treatment and 15 whose HIV infection had totally stalled. This last group included nonprogressors so adept at halting an HIV infection that they didn’t even have any virus detectable by routine tests. (Researchers ascertained infection by testing for antibodies to HIV.) Scientists call this subset of patients elite controllers. “They comprise 1 percent or fewer of HIV-infected people,” Lichterfeld says.
The researchers obtained immune cells called CD4 T cells — the prime targets of HIV — from all the volunteers and subjected these cells to lab tests. The tests showed that elite controllers had CD4 T cells that made 10 to 100 times more p21 than did people in the other three groups. “It’s not a subtle difference. It’s quite striking,” Lichterfeld says.
When the researchers put these cells in lab dishes and subjected them to an HIV assault, the cells loaded with p21 held off the virus.
"These data suggest that this protein can inhibit HIV,” Lichterfeld says. But he notes that the mechanism by which p21 does this and even how these cells make extra amounts of the protein are not yet fully understood. There may be genetic variations involved, he says.
This is exciting and may lead to remedies that help combat AIDS in the rest of the patients that don’t produce the copious p21 protein.