GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:18850004
| Citation |
Mottet, D, Pirotte, S, Lamour, V, Hagedorn, M, Javerzat, S, Bikfalvi, A, Bellahcène, A, Verdin, E and Castronovo, V (2009) HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene 28:243-56 |
|---|---|
| Abstract |
Cancer cells have complex, unique characteristics that distinguish them from normal cells, such as increased growth rates and evasion of anti-proliferative signals. Global inhibition of class I and II histone deacetylases (HDACs) stops cancer cell proliferation in vitro and has proven effective against cancer in clinical trials, at least in part, through transcriptional reactivation of the p21(WAF1/Cip1)gene. The HDACs that regulate p21(WAF1/Cip1) are not fully identified. Using small interfering RNAs, we found that HDAC4 participates in the repression of p21(WAF1/Cip1) through Sp1/Sp3-, but not p53-binding sites. HDAC4 interacts with Sp1, binds and reduces histone H3 acetylation at the Sp1/Sp3 binding site-rich p21(WAF1/Cip1) proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21(WAF1/Cip1). Induction of p21(WAF1/Cip1) mediated by silencing of HDAC4 arrested cancer cell growth in vitro and inhibited tumor growth in an in vivo human glioblastoma model. Thus, HDAC4 could be a useful target for new anti-cancer therapies based on selective inhibition of specific HDACs. |
| Links |
PubMed Online version:10.1038/onc.2008.371 |
| Keywords |
Acetylation; Animals; Binding Sites; Bone Neoplasms/pathology; Brain Neoplasms/drug therapy; Brain Neoplasms/pathology; Cell Line, Tumor/metabolism; Chick Embryo; Cyclin-Dependent Kinase Inhibitor p21/biosynthesis; Cyclin-Dependent Kinase Inhibitor p21/genetics; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glioblastoma/drug therapy; Glioblastoma/pathology; HeLa Cells/drug effects; HeLa Cells/metabolism; Histone Deacetylase Inhibitors; Histone Deacetylases/physiology; Histones/metabolism; Humans; Neoplasm Proteins/antagonists & inhibitors; Neoplasm Proteins/physiology; Osteosarcoma/pathology; Protein Processing, Post-Translational; RNA, Messenger/biosynthesis; RNA, Neoplasm/biosynthesis; Repressor Proteins/antagonists & inhibitors; Repressor Proteins/physiology; Sp1 Transcription Factor/physiology; Tumor Suppressor Protein p53/antagonists & inhibitors; Tumor Suppressor Protein p53/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
HUMAN:SP1 |
enables |
GO:0000976: transcription cis-regulatory region binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
HUMAN:SP1 |
enables |
GO:0042826: histone deacetylase binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q13547 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:SP1 |
enables |
GO:0042826: histone deacetylase binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P56524 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:HDAC4 |
contributes_to |
GO:0000976: transcription cis-regulatory region binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
involved_in |
GO:0006338: chromatin remodeling |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
involved_in |
GO:0043433: negative regulation of DNA-binding transcription factor activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
involved_in |
GO:0016575: histone deacetylation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
involved_in |
GO:0008284: positive regulation of cell population proliferation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
involved_in |
GO:0000122: negative regulation of transcription by RNA polymerase II |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:HDAC4 |
enables |
GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P08047 |
F |
Seeded From UniProt |
complete | |
|
enables |
GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P08047 |
F |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0008285: negative regulation of cell population proliferation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0008134: transcription factor binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P08047 |
F |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0000122: negative regulation of transcription by RNA polymerase II |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
See Help:References for how to manage references in GONUTS.
