Sic1 Homologue in Human and Diseases
The protein p27Kip1 is a human homologue of Sic1, both having a conserved inhibitory domain, but p27Kip1 inhibits G1 cyclins and not cyclin B. There are several human diseases that are linked to p27Kip1 and other cyclin kinase inhibitors:
- All Papillary microcarcinomas (PMCs) of the thyroid have a lower expression of p27Kip1 than normal thyroid tissue. Additionally, the expression of p27Kip1 in more aggressive, metastasising Papillary microcarcinomas is strongly reduced compared to nonmetastasing microcarcinomas. These results suggest that p27Kip1 acts as a tumor suppressor.
- Kaposi's sarcoma is a type of cancer which appears in combination with AIDS and presumably is caused by the human herpesvirus 8 (HHV8). This virus expresses a viral cyclin which builds a complex with Cdk6. This KSHV-cyclin-Cdk6 complex phosphorylates and destabilises p27Kip1, which results in a low level of p27Kip1. This suggests that the degradation of p27Kip1 is associated with the development of the tumors.
- Patients with a gastric adenocarcinoma (stomach cancer) have a higher chance of survival if the tumor has high p27Kip1 expression. Low p27Kip1 expression can lead to tumor de-differentiation, increased penetration through the gastric wall, lymph node metastasis and advanced tumor stage.
Thus, the human Cdk inhibitor p27Kip1 is a potential tumor suppressor protein. If its expression is reduced, the result might be unregulated progression from G1 to S-phase which deregulates cell division and simplifies the formation of tumors.
Read more about this topic: Sic1
Famous quotes containing the words human and/or diseases:
“Knowing how beleaguered working mothers truly are—knowing because I am one of them—I am still amazed at how one need only say “I work” to be forgiven all expectation, to be assigned almost a handicapped status that no decent human being would burden further with demands. “I work” has become the universally accepted excuse, invoked as an all-purpose explanation for bowing out, not participating, letting others down, or otherwise behaving inexcusably.”
—Melinda M. Marshall (20th century)
“The fantasies inspired by TB in the last century, by cancer now, are responses to a disease thought to be intractable and capricious—that is, a disease not understood—in an era in which medicine’s central premise is that all diseases can be cured.”
—Susan Sontag (b. 1933)