PMID- 12624111
OWN - NLM
STAT- MEDLINE
DCOM- 20030707
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 21
DP  - 2003 May 23
TI  - Small molecule modulators of histone acetyltransferase p300.
PG  - 19134-40
AB  - Histone acetyltransferases (HATs) are a group of enzymes that play a significant 
      role in the regulation of gene expression. These enzymes covalently modify the 
      N-terminal lysine residues of histones by the addition of acetyl groups from 
      acetyl-CoA. Dysfunction of these enzymes is often associated with the 
      manifestation of several diseases, predominantly cancer. Here we report that 
      anacardic acid from cashew nut shell liquid is a potent inhibitor of p300 and 
      p300/CBP-associated factor histone acetyltranferase activities. Although it does 
      not affect DNA transcription, HAT-dependent transcription from a chromatin 
      template was strongly inhibited by anacardic acid. Furthermore, we describe the 
      design and synthesis of an amide derivative 
      N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) 
      using anacardic acid as a synthon, which remarkably activates p300 HAT activity 
      but not that of p300/CBP-associated factor. Although CTPB does not affect DNA 
      transcription, it enhances the p300 HAT-dependent transcriptional activation from 
      in vitro assembled chromatin template. However, it has no effect on histone 
      deacetylase activity. These compounds would be useful as biological switching 
      molecules for probing into the role of p300 in transcriptional studies and may 
      also be useful as new chemical entities for the development of anticancer drugs.
FAU - Balasubramanyam, Karanam
AU  - Balasubramanyam K
AD  - Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, 
      Jawaharlal Nehru Center for Advanced Scientific Research, Jakkur, Bangalore 
      560064, India.
FAU - Swaminathan, V
AU  - Swaminathan V
FAU - Ranganathan, Anupama
AU  - Ranganathan A
FAU - Kundu, Tapas K
AU  - Kundu TK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030306
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Anacardic Acids)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chromatin)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histones)
RN  - 0 (N-(4-chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide)
RN  - 0 (Plant Extracts)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Salicylates)
RN  - 0 (Transcription Factors)
RN  - 18654-18-7 (anacardic acid)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.3.1.48 (p300-CBP-associated factor)
SB  - IM
MH  - Acetylation
MH  - Acetyltransferases/*antagonists & inhibitors/*metabolism/pharmacology
MH  - Amino Acid Sequence
MH  - *Anacardic Acids
MH  - Anacardium/chemistry
MH  - Antineoplastic Agents
MH  - Benzamides/chemical synthesis/pharmacology
MH  - Cell Cycle Proteins/*antagonists & inhibitors/*metabolism/pharmacology
MH  - Chromatin/genetics
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme Inhibitors/*pharmacology
MH  - HeLa Cells
MH  - Histone Acetyltransferases
MH  - Histones/chemistry/metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Molecular Structure
MH  - Plant Extracts/chemistry
MH  - Recombinant Proteins
MH  - Salicylates/chemistry/*pharmacology
MH  - Seeds/chemistry
MH  - Templates, Genetic
MH  - Transcription Factors
MH  - Transcription, Genetic/drug effects
MH  - p300-CBP Transcription Factors
EDAT- 2003/03/08 04:00
MHDA- 2003/07/08 05:00
CRDT- 2003/03/08 04:00
PHST- 2003/03/08 04:00 [pubmed]
PHST- 2003/07/08 05:00 [medline]
PHST- 2003/03/08 04:00 [entrez]
AID - S0021-9258(20)80137-9 [pii]
AID - 10.1074/jbc.M301580200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 May 23;278(21):19134-40. doi: 10.1074/jbc.M301580200. Epub 2003 
      Mar 6.