BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination

Liao, Shengjie; Du, Rong; Wang, Lei; Qu, Zhen; Cui, Xiukun; Li, Chang; Liu, Fei; Mi, Huang; Wang, Jiuxiang; Chen, Jiaxiang; Gao, Meng; Yu, Shanshan; Tang, Zhaohui; Li, David Wan Cheng; Jiang, Tao; Liu, Mugen

doi:10.1016/j.biocel.2015.08.016

Cited by 10 publications

(7 citation statements)

References 39 publications

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“…In unbiased mass spectrometric (MS) screens, five ubiquitination target lysines on HSF2 have been identified (Kim et al 2007;Wagner et al 2011), whereas ubiquitination of HSF4 is mainly targeted to K206 and appears to inhibit its transcriptional activity (Fig. 2; Liao et al 2015).…”

Section: Posttranslational Regulation Of Hsfsmentioning

confidence: 99%

Tailoring of Proteostasis Networks with Heat Shock Factors

Joutsen

Sistonen

2018

Cold Spring Harb Perspect Biol

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Section: Posttranslational Regulation Of Hsfsmentioning

confidence: 99%

Tailoring of Proteostasis Networks with Heat Shock Factors

Joutsen

Sistonen

2018

Cold Spring Harb Perspect Biol

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“… 18 BCAS2 has other physiological roles, such as acting as a negative regulatory factor in heat-shock factor 4 protein homoeostasis. 19 Because it interacts with the RPA complex and modulates ATR activation during DNA repair, 20 it is essential in maintaining genome integrity in mouse early embryos. 21 …”

Section: Introductionmentioning

confidence: 99%

BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair

et al. 2020

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Background Breast cancer amplified sequence 2 (BCAS2) plays crucial roles in pre-mRNA splicing and androgen receptor transcription. Previous studies suggested that BCAS2 is involved in double-strand breaks (DSB); therefore, we aimed to characterise its mechanism and role in prostate cancer (PCa). Methods Western blotting and immunofluorescence microscopy were used to assay the roles of BCAS2 in the DSBs of PCa cells and apoptosis in Drosophila, respectively. The effect of BCAS2 dosage on non-homologous end joining (NHEJ) and homologous recombination (HR) were assayed by precise end-joining assay and flow cytometry, respectively. Glutathione-S-transferase pulldown and co-immunoprecipitation assays were used to determine whether and how BCAS2 interacts with NBS1. The expression of BCAS2 and other proteins in human PCa was determined by immunohistochemistry. Results BCAS2 helped repair radiation-induced DSBs efficiently in both human PCa cells and Drosophila. BCAS2 enhanced both NHEJ and HR, possibly by interacting with NBS1, which involved the BCAS2 N-terminus as well as both the NBS1 N- and C-termini. The overexpression of BCAS2 was significantly associated with higher Gleason and pathology grades and shorter survival in patients with PCa. Conclusion BCAS2 promotes two DSB repair pathways by interacting with NBS1, and it may affect PCa progression.

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“…Furthermore, it was reported that BCAS2 interacted and negatively regulated HSF4 protein stability and transcription regulatory activity [51]. Mechanistically, it was demonstrated that BCAS2 mediated HSF4 proteasomal degradation via the ubiquitination of lysine 206 residue [51]. In line with this, either BCAS2 depletion or the substitution of lysine to arginine at this position (K206R) reduced HSF4 ubiquitination that in turn increased HSF4 protein stability [51].…”

Section: Post-translational Modificationsmentioning

confidence: 94%

“…Other than being the subject of phosphorylation by protein kinases, HSF4b could also be the target of dephosphorylation by ERK-specific dual-specificity phosphatase 26 (DUSP26), whereby the phosphorylation and dephosphorylation status of HSF4b would alter its transcriptional regulatory activities [50]. Furthermore, it was reported that BCAS2 interacted and negatively regulated HSF4 protein stability and transcription regulatory activity [51]. Mechanistically, it was demonstrated that BCAS2 mediated HSF4 proteasomal degradation via the ubiquitination of lysine 206 residue [51].…”

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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BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination

Cited by 10 publications

References 39 publications

Tailoring of Proteostasis Networks with Heat Shock Factors

Tailoring of Proteostasis Networks with Heat Shock Factors

BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair

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

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