Abstract
Stat3, a member of the signal transducers and activators of transcription (STAT) family, is a key signal transduction protein activated by numerous cytokines, growth factors, and oncoproteins that controls cell proliferation, differentiation, development, survival, and inflammation. Constitutive activation of Stat3 has been found frequently in a wide variety of human tumors and induces cellular transformation and tumor formation. In this study, we demonstrated that LIGHT, a member of tumor necrosis factor superfamily, activates Stat3 in cancer cells. LIGHT induces dose-dependent activation of Stat3 by phosphorylation at both the tyrosine 705 and serine 727 residues. The activation of Stat3 by LIGHT appears to be mediated by NIK phosphorylation. Expression of a kinase-inactive NIK mutant abolished LIGHT induced Stat3 activation. Overexpression of an active NIK induces Stat3 activation by phosphorylation at the both tyrosine 705 and serine 727 residues. Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays. In addition, LIGHT increases the expression of Stat3 target genes including cyclin D1, survivin, and Bcl-xL, and stimulates human LNCaP prostate cancer cell growth in vitro which can be blocked by expression of a dominant-negative Stat3 mutant. Taken together, these results indicate that in addition to activating NF-κB/p52, LIGHT also activates Stat3. Activation of Stat3 together with activating non-canonical NF-κB/p52 signaling by LIGHT may maximize its effects on cellular proliferation, survival, and inflammation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 379-384 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 359 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 27 2007 |
| Externally published | Yes |
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Keywords
- LIGHT
- NIK
- Prostate
- Stat3
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
LIGHT, a member of the TNF superfamily, activates Stat3 mediated by NIK pathway. / Nadiminty, Nagalakshmi; Chun, Jae Yeon; Hu, Yan; Dutt, Smitha; Lin, Xin; Gao, Allen C.
In: Biochemical and Biophysical Research Communications, Vol. 359, No. 2, 27.07.2007, p. 379-384.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LIGHT, a member of the TNF superfamily, activates Stat3 mediated by NIK pathway
AU - Nadiminty, Nagalakshmi
AU - Chun, Jae Yeon
AU - Hu, Yan
AU - Dutt, Smitha
AU - Lin, Xin
AU - Gao, Allen C
PY - 2007/7/27
Y1 - 2007/7/27
N2 - Stat3, a member of the signal transducers and activators of transcription (STAT) family, is a key signal transduction protein activated by numerous cytokines, growth factors, and oncoproteins that controls cell proliferation, differentiation, development, survival, and inflammation. Constitutive activation of Stat3 has been found frequently in a wide variety of human tumors and induces cellular transformation and tumor formation. In this study, we demonstrated that LIGHT, a member of tumor necrosis factor superfamily, activates Stat3 in cancer cells. LIGHT induces dose-dependent activation of Stat3 by phosphorylation at both the tyrosine 705 and serine 727 residues. The activation of Stat3 by LIGHT appears to be mediated by NIK phosphorylation. Expression of a kinase-inactive NIK mutant abolished LIGHT induced Stat3 activation. Overexpression of an active NIK induces Stat3 activation by phosphorylation at the both tyrosine 705 and serine 727 residues. Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays. In addition, LIGHT increases the expression of Stat3 target genes including cyclin D1, survivin, and Bcl-xL, and stimulates human LNCaP prostate cancer cell growth in vitro which can be blocked by expression of a dominant-negative Stat3 mutant. Taken together, these results indicate that in addition to activating NF-κB/p52, LIGHT also activates Stat3. Activation of Stat3 together with activating non-canonical NF-κB/p52 signaling by LIGHT may maximize its effects on cellular proliferation, survival, and inflammation.
AB - Stat3, a member of the signal transducers and activators of transcription (STAT) family, is a key signal transduction protein activated by numerous cytokines, growth factors, and oncoproteins that controls cell proliferation, differentiation, development, survival, and inflammation. Constitutive activation of Stat3 has been found frequently in a wide variety of human tumors and induces cellular transformation and tumor formation. In this study, we demonstrated that LIGHT, a member of tumor necrosis factor superfamily, activates Stat3 in cancer cells. LIGHT induces dose-dependent activation of Stat3 by phosphorylation at both the tyrosine 705 and serine 727 residues. The activation of Stat3 by LIGHT appears to be mediated by NIK phosphorylation. Expression of a kinase-inactive NIK mutant abolished LIGHT induced Stat3 activation. Overexpression of an active NIK induces Stat3 activation by phosphorylation at the both tyrosine 705 and serine 727 residues. Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays. In addition, LIGHT increases the expression of Stat3 target genes including cyclin D1, survivin, and Bcl-xL, and stimulates human LNCaP prostate cancer cell growth in vitro which can be blocked by expression of a dominant-negative Stat3 mutant. Taken together, these results indicate that in addition to activating NF-κB/p52, LIGHT also activates Stat3. Activation of Stat3 together with activating non-canonical NF-κB/p52 signaling by LIGHT may maximize its effects on cellular proliferation, survival, and inflammation.
KW - LIGHT
KW - NIK
KW - Prostate
KW - Stat3
UR - http://www.scopus.com/inward/record.url?scp=34249931559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249931559&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.05.119
DO - 10.1016/j.bbrc.2007.05.119
M3 - Article
C2 - 17543278
AN - SCOPUS:34249931559
VL - 359
SP - 379
EP - 384
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -