Downregulation of heat shock factor 4 transcription activity via MAPKinase phosphorylation at Serine 299

Cui, Xiukun; Han, Jiuli; Li, Jing; Cui, Wenwen; Wu, Dandan; Liu, Shiyuan; Xue, Wenxian; Wang, Xiangxiang; Ma, Yi; Zhang, Jing; Zhang, Jun; Mu, Hongmei; Zhang, Fengyan; Hu, Yanzhong

doi:10.1016/j.biocel.2018.10.003

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…Heat shock factor 4, which contains conserved DNA binding and trimerization domains, is a vital member of HSFs. Recent studies revealed that dysregulation of HSF4 expression could result in carcinogenesis 15,16 . Moreover, HSF4 was also reported to regulate several important biological function of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

Tang

et al. 2020

Liver International

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Background and Aims: Heat shock factor (HSF4) plays a vital role in carcinogenesis and tumour progression. However, its clinical significance implications in hepatocellular carcinoma (HCC) remained elusive.Methods: RT-PCR and western blot were used to detect the HSF4 expression levels in HCC cells and tissues. Immunohistochemistry staining was performed on a tissue microarray containing 104 HCC patients received radical resection. In vitro effects of HSF4 on proliferation, migration and invasion were determined by colony formation and transwell assays in HCCLM3, Huh7, MHCC97L and SMMC7721 cells. Epithelialmesenchymal transition (EMT) was identified by RT-PCR, WB and immunofluorescence in HCCLM3 and MHCC97L cells. AKT pathway activation was detected by WB and dual luciferase report system in HCCLM3 and MHCC97L cells.Results: HSF4 expression was higher in primary HCC tissues derived from recurrent patients, and positively correlated with invasiveness potentials of cell lines. Clinically,

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Section: Introductionmentioning

confidence: 99%

HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

Tang

et al. 2020

Liver International

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“…The phosphorylation of S299 is responsible for tuning down HSF4 transcriptional activity [ 10 ]. The EGF-EGFR-ERK1/2 pathway is able to phosphorylate K299, resulting in the downregulation of αB-crystallin and HSP25 expression in mouse lens [ 11 ]. The amino acids S299 and K294 make up the PDSM motif in HSF4b, and the phosphorylation of S299 can trigger K294 sumoylation in vitro [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Its divergent transcriptional activities are regulated by posttranslational modifications (e.g. phosphorylation and sumoylation) [ 10 , 11 ] as well as other associated proteins such as BCSA2 [ 12 ] and dual specific protein phosphatase 26 (DUSP26) [ 13 ]. HSF4b associates with and is phosphorylated by ERK1/2 and P38, which results in Hsf4b protein stabilization.…”

Section: Introductionmentioning

confidence: 99%

“…The growth factor FGF2, which is important for early lens development, increases Hsf4b protein stabilization by activating ERK1/2-mediated phosphorylation and/or sumoylation [ 14 , 15 ]. EGF activates ERK-mediated phosphorylation of HSF4 at S299, which attenuates HSF4b-controlled aB-crystallin expression in lens in vitro [ 11 ]. The mutation analysis indicates that phosphorylation of S299 increases HSF4 interaction with transcriptional repressor Daxx [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation

Yan

et al. 2022

Biochemistry and Biophysics Reports

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“…The phosphorylation of the HSF4b serine 298 residue by mitogen-activated protein kinase (MAPK) ERK1/2 mediated the sumoylation of lysine at residue 293, which subsequently led to the suppression of HSF4b transcriptional activation function [46]. For instance, phosphorylation-mediated sumoylation of this HSF4b lysine residue reduced the expression of the crystallin gene, an important HSF4 downstream target that was involved in governing normal lens development and homeostasis [47]. On top of inhibiting HSF4b from activating the expression of its downstream targets, this specific modification could also promote HSF4b interaction with a transcriptional repressor to negatively regulate the expression of its target genes [48].…”

Section: Post-translational Modificationsmentioning

confidence: 99%

More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases

et al. 2021

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Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.

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Downregulation of heat shock factor 4 transcription activity via MAPKinase phosphorylation at Serine 299

Cited by 6 publications

References 23 publications

HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation

More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases

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