TY - JOUR
T1 - Depletion of histone deacetylase protein
T2 - A common consequence of inflammatory cytokine signaling?
AU - Vashisht Gopal, Y. N.
AU - Van Dyke, Michael W.
N1 - Funding Information:
This study was supported by the U.S. Department of Defense Breast Cancer Research Program grant W81XWH-04-1- 0610 to MWVD. We thank Dr. Elizabeth Grimm for the gift of IFNγ cytokine.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - The dynamics of histone acetylation and deacetylation have long been known to influence gene expression by cellular signaling pathways. However, the mechanisms that regulate histone acetyl transferases (HATs) and histone deacetylases (HDACs) by these pathways have only recently become the focus of scientific investigation, spurred by increasing knowledge that HDACs can promote cancer growth. We recently reported that pro-inflammatory signals such as tumor necrosis factor α (TNFα) induce HDAC1 ubiquitination and proteasomal degradation through the IκB kinase IKKκ. The resulting depletion of cellular HDAC1 levels lead to a consequent depletion of HDAC1 associated with the CDKN1A gene promoter and increased expression of its protein product, p21WAF1/CIP1. This phenomenon heralds a unique mechanism of HDAC regulation that modulates the pro-inflammatory activity of TNFα and other cytokines at the level of gene expression. Here we discuss the current knowledge of pro-inflammatory cytokine-induced regulation of gene expression, emphasizing the involvement of HDAC1, and its possible implications in inflammation, cancer, and their therapy.
AB - The dynamics of histone acetylation and deacetylation have long been known to influence gene expression by cellular signaling pathways. However, the mechanisms that regulate histone acetyl transferases (HATs) and histone deacetylases (HDACs) by these pathways have only recently become the focus of scientific investigation, spurred by increasing knowledge that HDACs can promote cancer growth. We recently reported that pro-inflammatory signals such as tumor necrosis factor α (TNFα) induce HDAC1 ubiquitination and proteasomal degradation through the IκB kinase IKKκ. The resulting depletion of cellular HDAC1 levels lead to a consequent depletion of HDAC1 associated with the CDKN1A gene promoter and increased expression of its protein product, p21WAF1/CIP1. This phenomenon heralds a unique mechanism of HDAC regulation that modulates the pro-inflammatory activity of TNFα and other cytokines at the level of gene expression. Here we discuss the current knowledge of pro-inflammatory cytokine-induced regulation of gene expression, emphasizing the involvement of HDAC1, and its possible implications in inflammation, cancer, and their therapy.
KW - Deacetylation
KW - HDAC1
KW - Pro-inflammatory cytokine
KW - Proteasomal degradation
KW - TNFα
UR - http://www.scopus.com/inward/record.url?scp=33845419558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845419558&partnerID=8YFLogxK
U2 - 10.4161/cc.5.23.3522
DO - 10.4161/cc.5.23.3522
M3 - Review article
C2 - 17172847
AN - SCOPUS:33845419558
SN - 1538-4101
VL - 5
SP - 2738
EP - 2743
JO - Cell Cycle
JF - Cell Cycle
IS - 23
ER -