Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 21 April 2012, last major update January 2012
Copyright: (c) 2012, PathologyOutlines.com, Inc.
● Silent Information Regulator Transcript 1
● Encodes a member of the sirtuin family of proteins
● Nicotinamide adenine dinucleotide (NAD) dependent deacetylase
● Can both promote and suppress tumorigenesis (N A J Med Sci 2011;4:104)
● Energy metabolism: senses energy/nutrient status via NAD+/NADH ratio, functions as transcriptional repressor via histone deacetylation in the nucleus; modifies acetylation level of p53, NF-KB, FOX0; SIRT1 activation stimulates PGC1α, which activates mitochondrial biogenesis and metabolism and increases insulin sensitivity (Nutr Metab (Lond) 2011;8:91 [Epub ahead of print])
● BCR-ABL of CML activates SIRT1 expression in hematopoietic progenitor cells (Blood 2011 Dec 29 [Epub ahead of print])
● Important in epigenetic gene silencing; inhibition reactivates silenced genes; associated with CpG island methylator phenotype-high MSI-high colon cancer (Mod Pathol 2009;22:922)
Localization and functions of the human sirtuins Sirt1, Sirt2 and Sirt3
● Associated with poor prognosis in breast carcinoma (Hum Pathol 2011;42:204), and diffuse large B cell lymphoma (Am J Surg Pathol 2008;32:1523)
● Nuclear staining
Uses by pathologists
● None at this time
SIRT1 expression in colorectal cancer
Positive staining - disease
● Breast carcinoma (67%, Hum Pathol 2011;42:204)
● Diffuse large B cell lymphoma (74%, Am J Surg Pathol 2008;32:1523)
End of Stains > SIRT1
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