Identification of Mixed Lineage Leukemia 1(MLL1) Protein as a Coactivator of Heat Shock Factor 1(HSF1) Protein in Response to Heat Shock Protein 90 (HSP90) Inhibition

Chen, Yaoyu; Chen, Jinyun; Yu, Jianjun; Yang, Guizhi; Temple, Emilia; Harbinski, Fred; Gao, Hui; Wilson, Christopher J.; Pagliarini, Raymond; Zhou, Wenlai

doi:10.1074/jbc.m114.574053

Cited by 13 publications

(14 citation statements)

References 47 publications

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“…A small amount of the HSF1 trimer has been shown to constitutively bind to the HSP70 promoter in complex with replication protein A and the histone chaperone FACT (facilitates chromatin transcription) [6] and recruits poly(ADP‐ribose) polymerase PARP13‐PARP1 complex in advance [7]. During heat shock, activated HSF1 heavily occupies HSEs in the promoter, facilitating the redistribution of PARP1 within the HSP70 locus [7], and also recruits coactivators, including BRG1 [8], p300 [9], ASC‐2 [10], and [11] MLL1, which promote the establishment of an active chromatin state and the transcription of HSP70 in mammals. Promoter‐bound HSF1 also recruits other coactivators, including shugoshin 2 (SGO2) and the central coactivator complex Mediator [12], which facilitate the formation of the preinitiation complex (PIC) containing general transcription factors (GTFs) and RNA polymerase II (Pol II) [13].…”

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confidence: 99%

MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells

et al. 2021

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Activated and promoter-bound heat-shock transcription factor 1 (HSF1) induces RNA polymerase II recruitment upon heat shock, and this is facilitated by the core Mediator in Drosophila and yeast. Another Mediator module, CDK8 kinase module (CKM), consisting of four subunits including MED12 and CDK8, plays a negative or positive role in the regulation of transcription; however, its involvement in HSF1-mediated transcription remains unclear. We herein demonstrated that HSF1 interacted with MED12 and recruited MED12 and CDK8 to the HSP70 promoter during heat shock in mammalian cells. The kinase activity of CDK8 (and its paralog CDK19) promoted HSP70 expression partly by phosphorylating HSF1-S326 and maintained proteostasis capacity. These results indicate an important role for CKM in the protection of cells against proteotoxic stress.

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confidence: 99%

MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells

et al. 2021

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“…Furthermore, HSFs have been shown to recruit MLL-type complexes as co-activators in other contexts. 39,40 Although HSF-1 and SET-16/MLL3/4 appear to directly upregulate LET-70/E2, our results suggest that NHR-67/TLX can antagonize this activity, as nhr-67 mutations induce precocious, increased LET-70 linker cell expression. Cooperative interactions between MLL3/4 and nuclear hormone receptors have been recognized in the literature in several settings.…”

Section: Discussionmentioning

confidence: 65%

Transcriptional control of non-apoptotic developmental cell death in C. elegans

et al. 2016

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Programmed cell death is an essential aspect of animal development. Mutations in vertebrate genes that mediate apoptosis only mildly perturb development, suggesting that other cell death modes likely have important roles. Linker cell-type death (LCD) is a morphologically conserved cell death form operating during the development of Caenorhabditis elegans and vertebrates. We recently described a molecular network governing LCD in C. elegans, delineating a key role for the transcription factor heat-shock factor 1 (HSF-1). Although HSF-1 functions to protect cells from stress in many settings by inducing expression of protein folding chaperones, it promotes LCD by inducing expression of the conserved E2 ubiquitin-conjugating enzyme LET-70/UBE2D2, which is not induced by stress. Following whole-genome RNA interference and candidate gene screens, we identified and characterized four conserved regulators required for LCD. Here we show that two of these, NOB-1/Hox and EOR-1/PLZF, act upstream of HSF-1, in the context of Wnt signaling. A third protein, NHR-67/TLX/NR2E1, also functions upstream of HSF-1, and has a separate activity that prevents precocious expression of HSF-1 transcriptional targets. We demonstrate that the SET-16/mixed lineage leukemia 3/4 (MLL3/4) chromatin regulation complex functions at the same step or downstream of HSF-1 to control LET-70/UBE2D2 expression. Our results identify conserved proteins governing LCD, and demonstrate that transcriptional regulators influence this process at multiple levels.

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“…It also recruits PARP13‐PARP1 complex to prepare for the response (Fujimoto et al , ). During heat shock, activated HSF1 heavily occupies HSEs in the HSP70 promoter and dramatically induces its transcription (Vihervaara et al , ; Takii et al , ; Mahat et al , ), by recruiting various kinds of coactivators including ASC‐2 (Hong et al , ), MLL1 (Chen et al , ), and BRG1 (Sullivan et al , ; Corey et al , ), and by causing the redistribution of PARP1 (Fujimoto et al , ). These coactivators promote establishment of an active chromatin state and may thereby facilitate PIC formation during heat shock (Corey et al , ; Takii et al , ; Fujimoto et al , ).…”

Section: Introductionmentioning

confidence: 99%

The pericentromeric protein shugoshin 2 cooperates with HSF 1 in heat shock response and RNA Pol II recruitment

et al. 2019

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The recruitment of RNA polymerase II (Pol II) to core promoters is highly regulated during rapid induction of genes. In response to heat shock, heat shock transcription factor 1 (HSF1) is activated and occupies heat shock gene promoters. Promoter‐bound HSF1 recruits general transcription factors and Mediator, which interact with Pol II, but stress‐specific mechanisms of Pol II recruitment are unclear. Here, we show in comparative analyses of HSF1 paralogs and their mutants that HSF1 interacts with the pericentromeric adaptor protein shugoshin 2 (SGO2) during heat shock in mouse cells, in a manner dependent on inducible phosphorylation of HSF1 at serine 326, and recruits SGO2 to the HSP70 promoter. SGO2‐mediated binding and recruitment of Pol II with a hypophosphorylated C‐terminal domain promote expression of HSP70, implicating SGO2 as one of the coactivators that facilitate Pol II recruitment by HSF1. Furthermore, the HSF1‐SGO2 complex supports cell survival and maintenance of proteostasis in heat shock conditions. These results exemplify a proteotoxic stress‐specific mechanism of Pol II recruitment, which is triggered by phosphorylation of HSF1 during the heat shock response.

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Identification of Mixed Lineage Leukemia 1(MLL1) Protein as a Coactivator of Heat Shock Factor 1(HSF1) Protein in Response to Heat Shock Protein 90 (HSP90) Inhibition

Cited by 13 publications

References 47 publications

MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells

MED12 interacts with the heat‐shock transcription factor HSF1 and recruits CDK8 to promote the heat‐shock response in mammalian cells

Transcriptional control of non-apoptotic developmental cell death in C. elegans

The pericentromeric protein shugoshin 2 cooperates with HSF 1 in heat shock response and RNA Pol II recruitment

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