Selective STAT3-α or -β expression reveals spliceform-specific phosphorylation kinetics, nuclear retention and distinct gene expression outcomes

Probably not a substantial claim: may not pass S3 (load-bearing).

Initial support for STAT3β acting as a dominant-negative regulator came with the repression and/or down-regulation of a number of recognized STAT3α target genes when STAT3β was overexpressed.

“Initial support for this came with the repression and/or down-regulation of a number of recognized STAT3α target genes when STAT3β was overexpressed [10,48].”

• cites [10] Caldenhoven, 1996, STAT3β, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription, J. Biol. Chem. sourceNot checked — no full text of the source
• cites [48] Schaefer, 1995, Cooperative transcriptional activity of Jun and Stat3β, a short form of Stat3, Proc. Natl. Acad. Sci. U.S.A. sourceDisputed

  The Results report that overexpressed STAT3β stimulated the α2-macroglobulin–TK promoter; STAT3α, not STAT3β, slightly repressed reporter expression. The Discussion likewise describes STAT3β as activating this promoter, rather than acting as a dominant-negative regulator. Our copy does not report down-regulation of multiple STAT3α target genes by STAT3β. (LLM, conf=0.85)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Direct side-by-side comparisons of STAT3α phosphorylation in Stat3β−/−, Stat3β+/− or Stat3β+/+ cells were not presented in those studies, and the loss of STAT3 DNA binding or STAT3 reporter gene activity appeared to be greater than could be anticipated based solely on the ratios of STAT3α/STAT3β in WT cells.

“However, direct side-by-side comparisons of STAT3α phosphorylation in Stat3β−/−, Stat3β+/− or Stat3β+/+ cells were not presented in those studies and the loss of STAT3 DNA binding or STAT3 reporter gene activity appeared to be greater than could be anticipated based solely on the ratios of STAT3α/STAT3β in WT cells [16].”

• cites [16] Yoo, 2002, Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock, Cell sourceDisputed

  Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim. May combine two claims.

In vivo studies indicate a requirement for STAT3β during endotoxic assault, a requirement for STAT3α in IL-8 synthesis, and differential roles for STAT3α and STAT3β in anti-inflammatory responses.

“spliceform-specific functions have been indicated by various in vivo studies showing a requirement for STAT3β during endotoxic assault [16], but a requirement for STAT3α in IL-8 synthesis [17], as well as differential roles for STAT3α and STAT3β in anti-inflammatory responses [15].”

• cites [16] Yoo, 2002, Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock, Cell sourceSupported
• cites [17] Yeh, 2004, Oxidized phospholipids increase interleukin 8 (IL-8) synthesis by activation of the c-src/signal transducers and activators of transcription (STAT)3 pathway, J. Biol. Chem. sourcePartly supported

  The Abstract and Discussion report that STAT3 participates in Ox-PAPC-induced IL-8 synthesis in human endothelial cells; the Discussion says a dominant-negative STAT3β construct inhibited that response. The paper does not directly establish a specific requirement for STAT3α, and the reported experiment was in cultured cells, not in vivo. The other clauses of the citing sentence have separate citations and are not attributed to this source. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [15] Maritano, 2004, The STAT3 isoforms α and β have unique and specific functions, Nat. Immunol. sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

STAT3-dependent up-regulation of microRNAs (such as miR-21 and miR-181b-1) mediates repression of gene expression.

“such as those requiring STAT3-dependent up-regulation of microRNAs (such as miR-21 and miR-181b-1 [56]) that mediate repression of gene expression.”

• cites [56] Iliopoulos, 2010, STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer, Mol. Cell sourceSupported

May combine two claims.

These results are consistent with the association of STAT3 with both active and inactive promoters in embryonic stem cells and the reported actions of STAT3 to down-regulate expression of specific target genes, such as Necdin.

“These results are consistent with the association of STAT3 with both active and inactive promoters in embryonic stem cells [54] and the reported actions of STAT3 to down-regulate expression of specific target genes, such as that recently described for the negative growth regulator Necdin [55].”

• cites [54] Kidder, 2008, Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells, PLoS ONE sourceSupported
• cites [55] Haviland, 2011, Necdin, a negative growth regulator, is a novel STAT3 target gene down-regulated in human cancer, PLoS ONE sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

STAT3-dependent repression of genes has been shown to be critical for muscle cell differentiation.

“Similarly, the STAT3-dependent repression of genes has been shown to be critical for muscle cell differentiation [53].”

• cites [53] Snyder, 2008, Identification of novel direct Stat3 target genes for control of growth and differentiation, J. Biol. Chem. sourceSupported

Classified as probably not a substantial claim.

Basal STAT3 has been shown to have transcriptional activity under basal conditions.

“and that basal STAT3 has been shown to have transcriptional activity under basal conditions [44,45]”

• cites [44] Yang, 2005, Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation, Cancer Res. sourceSupported
• cites [45] Yang, 2007, Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFκB, Genes Dev. sourcePartly supported

  The section “RANTES expression is induced cooperatively by p65 and U-STAT3” reports transcriptional activity from unphosphorylated STAT3, including increased RANTES promoter activity. However, the experiments used overexpression of STAT3; they do not establish that STAT3 at basal levels has this activity under basal conditions. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Others have concluded that there were no noticeable changes in STAT3α regulation in the absence of STAT3β (i.e. in Stat3β−/− MEFs) following cytokine stimulation.

“Indeed, others have also concluded that there were no noticeable changes in STAT3α regulation in the absence of STAT3β (i.e. in Stat3β−/− MEFs) following cytokine stimulation [16].”

• cites [16] Yoo, 2002, Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock, Cell sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The prolonged nuclear retention of STAT3β observed in this study is consistent with an earlier report of nuclear retention of STAT3β following cell exposure to IL-6.

“This is consistent with an earlier report of nuclear retention of STAT3β following cell exposure to IL-6 [32].”

• cites [32] Huang, 2007, Stat3 isoforms, α and β, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3β mapping to its unique C-terminal end, J. Biol. Chem. sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Striking changes in the levels of STAT3α and STAT3β have been noted during myeloid differentiation.

“Given the striking changes in the levels of STAT3α and STAT3β noted during myeloid differentiation [12–14]”

• cites [12] Biethahn, 1999, Expression of granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor-associated signal transduction proteins of the JAK/STAT pathway in normal granulopoiesis and in blast cells of acute myelogenous leukemia, Exp. Hematol. sourceNot checked — no full text of the source
• cites [13] Dewilde, 2008, Of alphas and betas: distinct and overlapping functions of STAT3 isoforms, Front. Biosci. sourceSupported
• cites [14] Hevehan, 2002, Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation, Blood sourceNot checked — no full text of the source

May combine two claims.

Previously, the R609L mutation that disrupts the SH2 domain function of STAT3 has only been made in the context of STAT3α, but its expression in cells with endogenous STAT3α levels precluded its detailed characterization of phosphorylation and nuclear translocation kinetics.

“Previously, the R609L mutation that disrupts the SH2 domain function of STAT3 has only been made in the context of STAT3α, but its expression in cells with endogenous STAT3α levels precluded its detailed characterization of phosphorylation and nuclear translocation kinetics [29].”

• cites [29] Zhang, 2000, The coiled-coil domain of Stat3 is essential for its SH2 domain-mediated receptor binding and subsequent activation induced by epidermal growth factor and interleukin-6, Mol. Cell. Biol. sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

STAT3 has been demonstrated to activate or repress its direct target genes in NIH 3T3 cells, with OSM treatment increasing six of 18 direct target genes specifically tested, but decreasing expression of ten of these 18 direct target genes.

“Notably, STAT3 has been demonstrated to activate or repress its direct target genes in NIH 3T3 cells, with OSM treatment increasing six of 18 direct target genes specifically tested, but decreasing expression of ten of these 18 direct target genes [53].”

• cites [53] Snyder, 2008, Identification of novel direct Stat3 target genes for control of growth and differentiation, J. Biol. Chem. sourceSupported

Classified as probably not a substantial claim. May combine two claims.

Dimerization between STAT3 proteins is a prerequisite for nuclear translocation upon activation and occurs via its functional SH2 domain.

“Dimerization between STAT3 proteins has been a prerequisite for nuclear translocation upon activation and this interaction occurs via its functional SH2 domain [28,29].”

• cites [28] Shuai, 1994, Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions, Cell sourceNot checked — no full text of the source
• cites [29] Zhang, 2000, The coiled-coil domain of Stat3 is essential for its SH2 domain-mediated receptor binding and subsequent activation induced by epidermal growth factor and interleukin-6, Mol. Cell. Biol. sourceSupported

Classified as probably not a substantial claim.

There has been increasing evidence of basal nucleocytoplasmic shuttling of STAT3.

“As there has been increasing evidence of basal nucleocytoplasmic shuttling of STAT3 [6,41–43]”

• cites [6] Liu, 2005, STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-α3, Proc. Natl. Acad. Sci. U.S.A. sourceNot checked — no full text of the source
• cites [41] Herrmann, 2007, Nucleocytoplasmic shuttling of persistently activated STAT3, J. Cell Sci. sourceNot checked — no full text of the source
• cites [42] Pranada, 2004, Real time analysis of STAT3 nucleocytoplasmic shuttling, J. Biol. Chem. sourceSupported
• cites [43] Vogt, 2011, The role of the N-terminal domain in dimerization and nucleocytoplasmic shuttling of latent STAT3, J. Cell Sci. sourceSupported

May combine two claims.

Under basal non-cytokine-stimulated conditions, phospho-STAT3 levels in iSTAT3α MEFs are significantly lower than in WT MEFs, whereas nuclear phospho-STAT3 levels in iSTAT3β MEFs are significantly higher.

“under basal non-cytokine-stimulated conditions, the levels of phospho-STAT3 detected in iSTAT3α MEFs were significantly lower than in WT MEFs, whereas the levels of nuclear phospho-STAT3 in iSTAT3β MEFs were significantly higher.”

May combine two claims. The quote only partly states this claim.

STAT3β regulates 39 genes classified in the GO term of developmental processes after OSM stimulation, while no genes in this GO category are altered in iSTAT3α MEFs.

“Further consideration of the GO lists showed the dominance of STAT3β to regulate genes classified in the GO term of developmental processes, with 39 genes (Supplementary Table S5 at http://www.BiochemJ.org/bj/447/bj4470125add.htm) altered in expression in iSTAT3β MEFs, but no genes in this GO category altered in iSTAT3α MEFs.”

May combine two claims.

In transiently transfected AD293 cells, FLAG-STAT3β shows a comparable increase in nuclear localization after 15 min of OSM treatment, but remains predominantly nuclear at 60 min whereas FLAG-STAT3α is cytoplasmic at 60 min.

“A comparable increase in nuclear localization of FLAG–STAT3β was observed following 15 min of OSM treatment, but strikingly FLAG–STAT3α showed cytoplasmic localization following 60 min of OSM treatment, whereas FLAG–STAT3β remained predominantly nuclear”

May combine two claims.

Following cytokine stimulation, STAT3β shows sustained nuclear translocation and phosphorylation, whereas STAT3α shows transient nuclear translocation and phosphorylation.

“Notably, the sustained nuclear translocation and phosphorylation of STAT3β following cytokine exposure contrasted with a transient nuclear translocation and phosphorylation of STAT3α.”

• Also stated in: § Enhanced Tyr705 phosphorylation and nuclear retention of STAT3β following cytokine stimulation · plain

  “showed the dominance of nuclear STAT3 following 15 min of OSM treatment, with an ensuing rapid loss of FLAG–STAT3α from the nucleus but nuclear retention of FLAG–STAT3β by 60 min of OSM treatment”

• Also stated in: § Enhanced Tyr705 phosphorylation and nuclear retention of STAT3β following cytokine stimulation · plain

  “nuclear levels of phospho-STAT3 were highest at 15 min post-activation with OSM in all cases in WT, iSTAT3α and iSTAT3β MEFs, and declined rapidly in the case of iSTAT3α MEFs.”

May combine two claims.

In WT MEFs, nuclear phospho-STAT3 is intense at 15 min of OSM stimulation and remains detectable at 60 min.

“noting the intense nuclear phospho-STAT3 detected at 15 min of OSM stimulation, but the continued detection of nuclear phospho-STAT3 following 60 min of OSM stimulation”

May combine two claims.

Some GO terms showed changes in iSTAT3α and iSTAT3β MEFs only, such as transport, cell organization and biogenesis or cell proliferation; conversely, some GO terms were restricted to iSTAT3α MEFs, such as cell cycle.

“Furthermore, some GO terms showed changes in iSTAT3α and iSTAT3β MEFs only, such as transport (Supplementary Table S3), cell organization and biogenesis (Supplementary Table S7 at http://www.BiochemJ.org/bj/447/bj4470125add.htm) or cell proliferation (Supplementary Table S8 at http://www.BiochemJ.org/bj/447/bj4470125add.htm). Conversely, some GO terms were restricted to iSTAT3α MEFs, such as cell”

The quote only partly states this claim.

In the GO term cell adhesion, three genes (Thbs1, Fbln2 and Cyr61) were regulated exclusively in the iSTAT3β MEFs after OSM stimulation.

“Similarly, in the GO term cell adhesion, three genes (Thbs1, Fbln2 and Cyr61) were regulated exclusively in the iSTAT3β MEFs.”

May combine two claims.

In transiently transfected AD293 cells, FLAG-STAT3α is largely cytosolic under basal conditions but predominantly nuclear following 15 min of OSM stimulation.

“FLAG–STAT3α was largely cytosolic under basal conditions, but predominantly nuclear following 15 min of OSM stimulation”

May combine two claims.

An additional 37 genes were regulated by STAT3α re-expression and OSM stimulation, and an additional 17 were regulated by STAT3β re-expression and OSM stimulation.

“an additional 37 were regulated by STAT3α re-expression and OSM stimulation and an additional 17 were regulated by STAT3β re-expression and OSM stimulation.”

May combine two claims.

STAT3β re-expression under basal conditions results in 394 metabolism, 161 protein metabolism, 124 transport, and 113 cell organization and biogenesis STAT3β-specific gene changes.

“we noted prominent representation of several GO classes: metabolism (394 STAT3β-specific changes), protein metabolism (161 STAT3β-specific changes), transport (124 STAT3β-specific changes) as well as cell organization and biogenesis (113 STAT3β-specific changes).”

May combine two claims.

STAT3β re-expression was sufficient to change the expression for genes for the GO class of cell death, but no genes in this class were uniquely regulated by STAT3α.

“Furthermore, STAT3β re-expression was sufficient to change the expression for genes for the GO class of cell death, but our statistical analyses showed that no genes in this class were uniquely regulated by STAT3α.”

May combine two claims.

Profiling the transcriptional consequences of re-expression of STAT3α or STAT3β in Stat3−/− MEFs revealed the range of gene expression changes shared by these STAT3 isoforms, but also large sets of STAT3β-specific differences under basal conditions.

“In profiling the transcriptional consequences of re-expression of STAT3α or STAT3β in Stat3−/− MEFs, our analysis revealed the range of gene expression changes shared by these STAT3 isoforms, but also large sets of STAT3β-specific differences under basal conditions.”

May combine two claims.

A functional SH2 domain of STAT3β is required for cross-regulation of STAT3α phosphorylation, consistent with the effects of STAT3β on STAT3α being dependent on STAT3 dimerization and/or phosphorylation.

“The results indicate the requirement for a functional SH2 domain of STAT3β in the cross-regulation of phosphorylation of STAT3α, consistent with the effects of STAT3β on STAT3α being dependent on STAT3 dimerization and/or phosphorylation.”

May combine two claims.

There is both functional overlap as well as unique roles for the two different STAT3 spliceforms.

“Thus there is both functional overlap as well as unique roles for these two different STAT3 spliceforms.”

May combine two claims.

STAT3α and STAT3β were expressed at comparable levels in the iSTAT3α and iSTAT3β MEF lines, allowing direct comparison of their functional effects without confounding by different expression levels.

“We have expressed STAT3α and STAT3β at comparable levels to facilitate a direct comparison of their functional effects”

• Also stated in: § Enhanced Tyr705 phosphorylation and nuclear retention of STAT3β following cytokine stimulation · plain

  “Our expression of each STAT3 spliceform was at a comparable level, thus allowing our direct comparison of their functional effects and biochemical actions attributable to their different C-terminal sequences without confounding effects of different levels of expression.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Phosphorylation of STAT3 Ser727 by serine/threonine kinases such as MAPKs enhances STAT3 transcriptional activity.

“whereas the phosphorylation of Ser727 by serine/threonine kinases such as the MAPKs (mitogen-activated protein kinases) enhances STAT3 transcriptional activity [5,6].”

• cites [5] Levy, 2002, What does Stat3 do?, J. Clin. Invest. sourceNot checked — no full text of the source
• cites [6] Liu, 2005, STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-α3, Proc. Natl. Acad. Sci. U.S.A. sourceNot checked — no full text of the source

May combine two claims.

STAT3β spliceform expression rescues STAT3−/− embryonic lethality, highlighting key STAT3β-specific roles in development.

“A previous study demonstrating rescue of STAT3−/− embryonic lethality with STAT3β spliceform expression (i.e. in the absence of STAT3α) highlight key STAT3β-specific roles in development [15].”

• cites [15] Maritano, 2004, The STAT3 isoforms α and β have unique and specific functions, Nat. Immunol. sourceNot checked — no full text of the source

May combine two claims.

The effects of STAT3β on transcription in response to cytokine exposure are not restricted to transcriptional repression, and the effects of STAT3α are not dominated by increased gene expression under these conditions.

“These results clearly illustrate that the effects of STAT3β on transcription in response to cytokine exposure are not restricted to transcriptional repression, and conversely that the effects of STAT3α are not dominated by increased gene expression under these conditions of analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Oligonucleotide-mediated enforced switching to preferential splicing of STAT3β has emphasized the anti-tumorigenic activity of STAT3β.

“a recent advance with an oligonucleotide-mediated enforced switching to preferential splicing of STAT3β (rather than STAT3α) has emphasized the anti-tumorigenic activity of STAT3β [18].”

• cites [18] Zammarchi, 2011, Antitumorigenic potential of STAT3 alternative splicing modulation, Proc. Natl. Acad. Sci. U.S.A. sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Activation of STAT3 requires phosphorylation of Tyr705 and Ser727.

“This activation of STAT3 requires the phosphorylation of Tyr705 and Ser727.”

• cites [5] Levy, 2002, What does Stat3 do?, J. Clin. Invest. sourceNot checked — no full text of the source
• cites [6] Liu, 2005, STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-α3, Proc. Natl. Acad. Sci. U.S.A. sourceNot checked — no full text of the source

May combine two claims.

STAT3α and STAT3β arise from alternative splicing; STAT3α is 92 kDa and 770 amino acids, whereas STAT3β is 84 kDa and identical except that 55 C-terminal amino acids are replaced by a unique seven-amino-acid sequence.

“Two distinct STAT3 isoforms originating from alternative splicing have been described. STAT3α (92 kDa) is 770 amino acids in length, whereas STAT3β (84 kDa) is identical in sequence with the exception of 55 amino acids at the C-terminal tail that are replaced with a unique seven-amino-acid sequence (Figure 1A) [10,11].”

• cites [10] Caldenhoven, 1996, STAT3β, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription, J. Biol. Chem. sourceNot checked — no full text of the source
• cites [11] Shao, 2001, Identification and characterization of cis elements in the STAT3 gene regulating STAT3 α and STAT3 β messenger RNA splicing, Blood sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Phosphorylation of STAT3 Tyr705 by JAKs is critical for STAT3 dimerization and subsequent cytokine-stimulated nuclear translocation.

“the phosphorylation of STAT3 Tyr705 by JAKs (Janus kinases) is critical for STAT3 dimerization and subsequent cytokine-stimulated nuclear translocation”

• cites [5] Levy, 2002, What does Stat3 do?, J. Clin. Invest. sourceNot checked — no full text of the source
• cites [6] Liu, 2005, STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-α3, Proc. Natl. Acad. Sci. U.S.A. sourceNot checked — no full text of the source

May combine two claims.

No known STAT3α regulators were identified in the genes significantly altered in expression by STAT3β, suggesting that the action of STAT3β to cross-regulate STAT3α is not dependent on longer-term transcriptional events.

“Importantly, in the context of understanding cross-regulation mechanisms, no known STAT3α regulators were identified in the genes significantly altered in expression by STAT3β, thus suggesting that the action of STAT3β to cross-regulate STAT3α is not dependent on longer-term transcriptional events.”

May combine two claims.

The regulation of STAT3α by STAT3β appears to require a functional STAT3β SH2 domain and/or the tyrosine phosphorylation of STAT3β.

“Thus the regulation of STAT3α by STAT3β appears to require a functional STAT3β SH2 domain and/or the tyrosine phosphorylation of STAT3β.”

Probably not a substantial claim: may not pass S3 (load-bearing).

STAT3 transcriptional activity has been attributed to its transactivation domain that binds transcription co-activators such as p300.

“STAT3 transcriptional activity has been attributed to its transactivation domain that binds transcription co-activators such as p300 [46].”

• cites [46] Schuringa, 2001, Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation, FEBS Lett. sourceNot checked — no full text of the source

May combine two claims.

These functions of STAT3β indicate its importance as a modulator of gene expression in its own right, and highlight the possibility that an additional important action of STAT3β may be in extending the activation kinetics for STAT3α.

“These functions of STAT3β indicate its importance as a modulator of gene expression in its own right, but also now highlight the exciting possibility that an additional important action of STAT3β may be in extending the activation kinetics for STAT3α.”

May combine two claims.

The present study reinforces the transcriptional functions of STAT3β under basal conditions as well as its direct actions to modulate STAT3α activation following cytokine stimulation.

“In conclusion, the present study reinforces the transcriptional functions of STAT3β under basal conditions as well as its direct actions to modulate STAT3α activation following cytokine stimulation.”

May combine two claims.

Both STAT3α and STAT3β are transcriptional regulators following cytokine stimulation, and STAT3β should not simply be viewed as a repressor or negative regulator of gene transcription.

“Thus both STAT3α and STAT3β are transcriptional regulators following cytokine stimulation, and STAT3β should not simply be viewed as a repressor or negative regulator of gene transcription.”

May combine two claims.

STAT3β is a potent transcriptional regulator with sustained nuclear retention and is also able to cross-regulate/enhance the transcriptional activity of STAT3α.

“Taken together, our results highlight that STAT3β is a potent transcriptional regulator with sustained nuclear retention and is also able to cross-regulate/enhance the transcriptional activity of STAT3α.”

May combine two claims.

STAT3β has been shown to initiate transcription of the p27Kip1 gene in myeloblastic cells, α1-anti-chymotrypsin and α2-macroglobulin in hepatocytes, and acute-phase genes in the liver during inflammation, and so can act as an up-regulator of transcription of specific gene sets.

“Furthermore, STAT3β has been shown to initiate transcription of the p27Kip1 gene in myeloblastic cells [51], α1-anti-chymotrypsin and α2-macroglobulin in hepatocytes [52], acute-phase genes in the liver during inflammation [15], and so can act as an up-regulator of transcription of specific gene sets.”

• cites [51] de Koning, 2000, STAT3-mediated differentiation and survival and of myeloid cells in response to granulocyte colony-stimulating factor: role for the cyclin-dependent kinase inhibitor p27Kip1, Oncogene sourceNot checked — no full text of the source
• cites [52] Sasse, 1997, Mutational analysis of acute-phase response factor/Stat3 activation and dimerization, Mol. Cell. Biol. sourceNot checked — no full text of the source
• cites [15] Maritano, 2004, The STAT3 isoforms α and β have unique and specific functions, Nat. Immunol. sourceNot checked — no full text of the source

May combine two claims.

The differences in gene expression profiles in the presence of the different STAT3 spliceforms, but also following cell exposure to cytokine, highlight further the remarkable spliceform-dependent differences in gene expression.

“The differences in gene expression profiles in the presence of the different STAT3 spliceforms, but also following cell exposure to cytokine, highlight further the remarkable spliceform-dependent differences in gene expression.”

May combine two claims.

The results highlight the large repertoire of STAT3α- and STAT3β-dependent changes, and that the STAT3β-dependent changes do not simply recapitulate the STAT3α-dependent changes observed.

“These results thus highlight the large repertoire of STAT3α- and STAT3β-dependent changes, and that the STAT3β-dependent changes do not simply recapitulate the STAT3α-dependent changes observed.”