Anti-aging protein SIRT1: A role in cervical cancer?

sirtuin protein SIRT1 is a well studied and highly complex NAD + dependent class III histone deacetylase that has seemingly diverse functions in metabolism, aging and cancer. SIRT1 deacetylates several downstream effector proteins including KU70, NBS1, the FOXO transcription factor family, and p53, several of which are in response to DNA damage events occurring within the cell [1]. Regulation of these factors by SIRT1 has indicated its direct role in cell growth and cellular senescence, and recent advances in understanding the physiologic nature of SIRT1 in these processes have posited both growth-promoting and grow-inhibiting effects of the protein. The transformative properties of the Human Papilloma Virus (HPV) were originally exploited well over 40 years ago as tools for elicudating mechanisms of cell growth control and cancerous transformation [2]. Indeed, the tumor suppressor p53 was first shown to be regulated by the ubiquitin-proteosome pathway by its association with the cellular ubiquitin ligase E6-AP, a protein upregulated by HPV E6 protein [3]. High risk HPV genotypes (HPV16,-18,-31, and-33) are now known as direct, causative agents of cervical cancer and the E6 and E7 proteins are widely known to induce the degradation and downregulation of p53 and pRb, respectively, as a mechanism for commendeering the growth of the host cell [4]. Until now, however, it has been unclear what other, if any, cellular factors HPV E6 This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited and E7 target for immortalizing cells. In this issue of Impact Aging, Allison et al. show that HPV E7 upregulates cellular SIRT1 and induces global histone modifications within the cell as an additional mechanism for promoting cell survival and inhibiting apoptosis. Significant research intensity has been placed on understanding the role SIRT1 has in cellular transformation and cancer with studies showing both growth-promoting and grow-inhibiting effects of the protein. It has been suggested that SIRT1 does not fit the classical definition of a bona fide tumor suppressor as it does not induce cell growth arrest when overexpressed in cell culture and has no documented cases of deleterious point mutations in any type of human tumor [5]. The growth suppressing observations in vivo, therefore, could be attributed to the genetic context of p53 [6]. In cells retaining wildtype p53, SIRT1 regulates and maintains p53 in …