Who watches the watchmen? Regulation of the expression and activity of sirtuins
2016; Wiley; Volume: 30; Issue: 12 Linguagem: Inglês
10.1096/fj.201600410rr
ISSN1530-6860
AutoresMarcin Buler, Jan Andersson, Jukka Hakkola,
Tópico(s)PARP inhibition in cancer therapy
ResumoSirtuins (SIRT1–7) are a family of nicotine adenine dinucleotide (NAD+)-dependent enzymes that catalyze post-translational modifications of proteins. Together, they regulate crucial cellular functions and are traditionally associated with aging and longevity. Dysregulation of sirtuins plays an important role in major diseases, including cancer andmetabolic, cardiac, andneurodegerativediseases. Theyare extensivelyregulatedinresponse to a wide range of stimuli, including nutritional and metabolic challenges, inflammatory signals or hypoxic and oxidative stress. Each sirtuin is regulated individually in a tissue- and cell-specific manner. The control of sirtuin expression involves all themajor points of regulation, including transcriptional and post-translationalmechanisms and microRNAs. Collectively, these mechanisms control the protein levels, localization, and enzymatic activity of sirtuins. In many cases, the regulators of sirtuin expression are also their substrates, which lead to formation of intricate regulatory networks and extensive feedback loops. In this review, we highlight themechanismsmediating thephysiologic andpathologic regulation of sirtuin expressionandactivity. We alsodiscuss the consequences of this regulation on sirtuin function and cellular physiology.—Buler, M., Andersson, U., Hakkola, J. Who watches the watchmen? Regulation of the expression and activity of sirtuins. FASEB J. 30, 3942–3960 (2016). www.fasebj.org
Referência(s)