Reactome | HDAC1:2-containing complex binds HDAC2 Inhibitors

HDAC1:2-containing complex binds HDAC2 Inhibitors

Stable Identifier

R-HSA-9679787

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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HDAC1:2-containing complex binds HDAC2 Inhibitors

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To carry out gene expression, a cell must control the winding and unwinding of DNA around histones. This is mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs). HDAC inhibitors inhibit the proliferation of tumour cells by inducing cell cycle arrest, differentiation and/or apoptosis (Zhang et al. 2019). Belinostat (Marks et al. 2000, O'Connor et al. 2015), vorinostat (Marks & Breslow 2007) and romidepsin (Ueda et al. 1994, VanderMolen et al. 2011) are HDAC inhibitors approved for the treatment of Peripheral T-cell lymphomas (PTCLs) (Hood & Shah 2016). These drugs are believed to bind to many, if not all HDAC proteins.

Human papillomaviruses (HPVs) cause epithelial proliferative diseases. The HDAC inhibitors vorinostat, belinostat and panobinostat have been shown to inhibit HPV DNA amplification and cause apoptosis in preclinical experiments (Banerjee et al. 2018).

The antiepileptic drug valproic acid inhibits HDAC2 and therefore is a promising drug for cancer therapy (Göttlicher et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
17211407	Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug Marks, PA, Breslow, R	Nat. Biotechnol.	2007
7513682	FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity Ueda, H, Nakajima, H, Hori, Y, Fujita, T, Nishimura, M, Goto, T, Okuhara, M	J. Antibiot.	1994
21587264	Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma VanderMolen, KM, McCulloch, W, Pearce, CJ, Oberlies, NH	J. Antibiot.	2011
10922406	Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells Marks, PA, Richon, VM, Rifkind, RA	J. Natl. Cancer Inst.	2000
11742974	Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells Göttlicher, M, Minucci, S, Zhu, P, Krämer, OH, Schimpf, A, Giavara, S, Sleeman, JP, Lo Coco, F, Nervi, C, Pelicci, PG, Heinzel, T	EMBO J	2001
26101246	Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study O'Connor, OA, Horwitz, S, Masszi, T, Van Hoof, A, Brown, P, Doorduijn, J, Hess, G, Jurczak, W, Knoblauch, P, Chawla, S, Bhat, G, Choi, MR, Walewski, J, Savage, K, Foss, F, Allen, LF, Shustov, A	J. Clin. Oncol.	2015