SIRT7 interacts with RNA polymerase I histones to promote Pol I-mediated rRNA transcription in the nucleolus . SIRT1 is the most studied sirtuin Ponatinib AP24534 family member, mainly due to its purported ability to promote longevity in yeast, worms, drosophila and mammals , , , . However its ability to increase the life span of lower organisms has recently been called into question . SIRT1 has also been suggested to have a critical role in tumorigenesis, however it is controversial whether SIRT1 is a tumor-suppressor or a tumor-promoter and in fact it is likely to be tumor-type specific . SIRT1′s deacetylase activity plays an important function in normal and malignant cellular processes by targeting histones, which results in a tighter chromatin structure and transcriptional repression .
Importantly, SIRT1 also modulates the stability and/or activation potential of a broad range of transcription factors, such as p53 , , FOXO , Ku70 , NF-��B , E2F1  and PPAR�� co-activator 1�� (PGC-1��)  and as recently described the hypoxia-inducible transcription factors (HIF), HIF-1  and HIF-2 . HIF transcription factors are the key mediators of oxygen homeostasis under hypoxic conditions and they play a vital role in embryonic development, physiological responses and in disease pathologies. HIF heterodimers are composed of an oxygen-sensitive ��-subunit and a constitutively expressed ��-subunit. HIF-1 and HIF-2 are the best-characterized isoforms and are mainly regulated by posttranslational modifications of their ��-subunit .
Specific prolyl hydroxylases (PHD), which depend on the substrates oxygen, Fe (II) and 2-oxoglutarate, target the ��-subunit under normoxic conditions . Hydroxylation of two proline residues (HIF-1��: P402 and P564 and HIF-2��: P405 and P531) within the oxygen-dependent degradation domain serve as a recognition site for the von Hippel-Lindau tumor suppressor (pVHL), a ubiquitin E3 ligase, which leads to the proteosomal degradation of the ��-subunit , , . In the absence of oxygen, PHDs are inactive and thereby HIF�� proteins are stabilized. Accumulated HIF�� protein translocates to the nucleus, forms a dimer with HIF�� and along with co-activators such as p300-CBP binds to hypoxia responsive elements (HRE) of target genes.
HIF-1 and HIF-2 share the same consensus sequence G/ACGTG in their target genes  and have several common gene targets such as erythropoietin (EPO), vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1) . However, they also have unique transcriptional targets, HIF-1 is responsible GSK-3 for the regulation of many genes encoding enzymes involved in the glycolytic pathway, as well as the pro-apoptotic gene BCL2 adenovirus E1B-interacting protein 1 (BNIP3) and carbonic anhydrase 9 (CA9) , .