Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 3121-3131 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biology |
| Volume | 32 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Aug 2012 |
| Externally published | Yes |
Keywords
- acyltransferase
- cyclin D
- histone methyltransferase
- histone methyltransferase mmset
- histone methyltransferase nsd2
- immunoglobulin enhancer binding protein
- interleukin 6
- interleukin 8
- methyltransferase
- protein bcl 2
- protein p300
- survivin
- tumor necrosis factor alpha
- unclassified drug
- vasculotropin A
- acetylation
- article
- autocrine effect
- cancer cell
- castration resistant prostate cancer
- cell proliferation
- cell survival
- chromatin
- controlled study
- enzyme activity
- gene targeting
- human
- human cell
- positive feedback
- priority journal
- promoter region
- protein expression
- protein interaction
- tumor growth
- Acetylation
- Animals
- Autocrine Communication
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
- Chromatin
- Cyclin D
- Gene Expression Regulation, Neoplastic
- Histone-Lysine N-Methyltransferase
- Histones
- Humans
- Inhibitor of Apoptosis Proteins
- Interleukin-6
- Interleukin-8
- Male
- Mice
- Mice, Inbred BALB C
- Neoplasm Transplantation
- NF-kappa B
- p300-CBP Transcription Factors
- Promoter Regions, Genetic
- Prostatic Neoplasms
- Proto-Oncogene Proteins c-bcl-2
- Repressor Proteins
- RNA Interference
- RNA, Small Interfering
- Signal Transduction
- Transplantation, Heterologous
- Tumor Necrosis Factor-alpha
- Vascular Endothelial Growth Factor A
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Histone methyltransferase NSD2/MMSET mediates constitutive NF-kb signaling for cancer cell proliferation, survival, and tumor growth via a feed-forward loop. / Yang, P.; Guo, L.; Duan, Z.J.; Tepper, C.G.; Xue, L.; Chen, X.; Kung, H.-J.; Gao, A.C.; Zou, J.X.; Chena, H.-W.
In: Molecular and Cellular Biology, Vol. 32, No. 15, 08.2012, p. 3121-3131.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Histone methyltransferase NSD2/MMSET mediates constitutive NF-kb signaling for cancer cell proliferation, survival, and tumor growth via a feed-forward loop
AU - Yang, P.
AU - Guo, L.
AU - Duan, Z.J.
AU - Tepper, C.G.
AU - Xue, L.
AU - Chen, X.
AU - Kung, H.-J.
AU - Gao, A.C.
AU - Zou, J.X.
AU - Chena, H.-W.
N1 - 引用次數:51 Export Date: 5 March 2018 CODEN: MCEBD 通訊地址: Zou, J.X.; UC Davis Cancer Center/Basic Sciences, University of California at Davis, Sacramento, CA, United States; 電子郵件: jxzou@ucdavis.edu 化學物質/CAS: acyltransferase, 9012-30-0, 9054-54-0; cyclin D, 146587-97-5; interleukin 8, 114308-91-7; methyltransferase, 9033-25-4; protein bcl 2, 219306-68-0; survivin, 195263-98-0; vasculotropin A, 489395-96-2; BIRC5 protein, human; Chromatin; Cyclin D; Histone-Lysine N-Methyltransferase, 2.1.1.43; Histones; Inhibitor of Apoptosis Proteins; Interleukin-6; Interleukin-8; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; RNA, Small Interfering; Repressor Proteins; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; WHSC1 protein, human, 2.1.1.43; p300-CBP Transcription Factors, 2.3.1.48; p300-CBP-associated factor, 2.3.1.48 參考文獻: Agoulnik, I.U., Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression (2005) Cancer Res, 65, pp. 7959-7967; Barish, G.D., Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response (2010) Genes Dev, 24, pp. 2760-2765; Caron, C., Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers (2010) Oncogene, 29, pp. 5171-5181; Carrozza, M.J., Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription (2005) Cell, 123, pp. 581-592; Chaturvedi, M.M., Sung, B., Yadav, V.R., Kannappan, R., Aggarwal, B.B., NF-kappaB addiction and its role in cancer: 'one size does not fit all. 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PY - 2012/8
Y1 - 2012/8
N2 - Constitutive NF-kB activation by proinflammatory cytokines plays a major role in cancer progression. However, the underlying mechanism is still unclear. We report here that histone methyltransferase NSD2 (also known as MMSET or WHSC1), a target of bromodomain protein ANCCA/ATAD2, acts as a strong coactivator of NF-kB by directly interacting with NF-kB for activation of target genes, including those for interleukin-6 (IL-6), IL-8, vascular endothelial growth factor A (VEGFA), cyclin D, Bcl-2, and survivin, in castration-resistant prostate cancer (CRPC) cells. NSD2 is recruited to the target gene promoters upon induction and mediates NF-kB activation-associated elevation of histone H3K36me2 and H3K36me3 marks at the promoter, which involves its methylase activity. Interestingly, we found that NSD2 is also critical for cytokine-induced recruitment of NF-kB and acetyltransferase p300 and histone hyperacetylation. Importantly, NSD2 is overexpressed in prostate cancer tumors, and its overexpression correlates with NF-kB activation. Furthermore, NSD2 expression is strongly induced by tumor necrosis factor alpha (TNF-α) and IL-6 via NF-kB and plays a crucial role in tumor growth. These results identify NSD2 to be a key chromatin regulator of NF-kB and mediator of the cytokine autocrine loop for constitutive NF-kB activation and emphasize the important roles played by NSD2 in cancer cell proliferation and survival and tumor growth. © 2012, American Society for Microbiology.
AB - Constitutive NF-kB activation by proinflammatory cytokines plays a major role in cancer progression. However, the underlying mechanism is still unclear. We report here that histone methyltransferase NSD2 (also known as MMSET or WHSC1), a target of bromodomain protein ANCCA/ATAD2, acts as a strong coactivator of NF-kB by directly interacting with NF-kB for activation of target genes, including those for interleukin-6 (IL-6), IL-8, vascular endothelial growth factor A (VEGFA), cyclin D, Bcl-2, and survivin, in castration-resistant prostate cancer (CRPC) cells. NSD2 is recruited to the target gene promoters upon induction and mediates NF-kB activation-associated elevation of histone H3K36me2 and H3K36me3 marks at the promoter, which involves its methylase activity. Interestingly, we found that NSD2 is also critical for cytokine-induced recruitment of NF-kB and acetyltransferase p300 and histone hyperacetylation. Importantly, NSD2 is overexpressed in prostate cancer tumors, and its overexpression correlates with NF-kB activation. Furthermore, NSD2 expression is strongly induced by tumor necrosis factor alpha (TNF-α) and IL-6 via NF-kB and plays a crucial role in tumor growth. These results identify NSD2 to be a key chromatin regulator of NF-kB and mediator of the cytokine autocrine loop for constitutive NF-kB activation and emphasize the important roles played by NSD2 in cancer cell proliferation and survival and tumor growth. © 2012, American Society for Microbiology.
KW - acyltransferase
KW - cyclin D
KW - histone methyltransferase
KW - histone methyltransferase mmset
KW - histone methyltransferase nsd2
KW - immunoglobulin enhancer binding protein
KW - interleukin 6
KW - interleukin 8
KW - methyltransferase
KW - protein bcl 2
KW - protein p300
KW - survivin
KW - tumor necrosis factor alpha
KW - unclassified drug
KW - vasculotropin A
KW - acetylation
KW - article
KW - autocrine effect
KW - cancer cell
KW - castration resistant prostate cancer
KW - cell proliferation
KW - cell survival
KW - chromatin
KW - controlled study
KW - enzyme activity
KW - gene targeting
KW - human
KW - human cell
KW - positive feedback
KW - priority journal
KW - promoter region
KW - protein expression
KW - protein interaction
KW - tumor growth
KW - Acetylation
KW - Animals
KW - Autocrine Communication
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cell Survival
KW - Chromatin
KW - Cyclin D
KW - Gene Expression Regulation, Neoplastic
KW - Histone-Lysine N-Methyltransferase
KW - Histones
KW - Humans
KW - Inhibitor of Apoptosis Proteins
KW - Interleukin-6
KW - Interleukin-8
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Neoplasm Transplantation
KW - NF-kappa B
KW - p300-CBP Transcription Factors
KW - Promoter Regions, Genetic
KW - Prostatic Neoplasms
KW - Proto-Oncogene Proteins c-bcl-2
KW - Repressor Proteins
KW - RNA Interference
KW - RNA, Small Interfering
KW - Signal Transduction
KW - Transplantation, Heterologous
KW - Tumor Necrosis Factor-alpha
KW - Vascular Endothelial Growth Factor A
U2 - 10.1128/MCB.00204-12
DO - 10.1128/MCB.00204-12
M3 - Article
VL - 32
SP - 3121
EP - 3131
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 15
ER -