A wikipedia of Dr. D'Adamo's research


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Histone deacetylases (HDAC) (EC number 3.5.1) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Deacetylation restores a positive electric charge, which increases the histone's affinity for DNA. This generally down-regulates DNA transcription by blocking the access of transcription factors.


HDAC inhibitors are being studied as a treatment for cancer. Richon et al. (1) found that HDAC inhibitors can induce p21 (WAF1) expression, a regulator of p53's tumor supressor activity. (2) HDACs are involved in the pathway by which the retinoblastoma protein (pRb) suppresses cell proliferation. The pRb protein is part of a complex which attracts HDACs to the chromatin so that it will deacetylate histones. (3)

HDAC inhibitors (HDIs) are also associated with the downregulation of some gene promoters. This could be due to upregulation of other, negative-regulatory proteins, however.

Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily. (4) (5)



1. Richon VM, Sandhoff TW, Rifkind RA, Marks PA. AUG 29 2000. "Histone deacetylase inhibitor selectively induces p21(WAF1) expression and gene-associated histone acetylation." Proceedings of the National Academy of Sciences of the United States of America 97(18):10014-10019.

2. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. NOV 19 1993. "WAF1, a potential mediator of p53 tumor suppression." Cell 75(4):817-25.

3. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. 1998 Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391(6667):597-601.

4. Leipe D.D., Landsman D. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. Nucleic Acids Res. 25: 3693-3697 (1997) PubMed 9278492.




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