Interaction of Hsp70 with p49/STRAP, a serum response factor binding protein

Lin, Jyun-Liang; Liu, Fu-Hwa; Wang, Chung

doi:10.1016/j.bbrc.2009.09.031

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…SRFBP1 is previously suggested to be a cofactor of SRF (serum response factor), contributing to the transcriptional regulation of cardiac genes during aging ( Zhang et al, 2004 ). Intriguingly, SRFBP1 is highly enriched in the nucleoli ( Lin et al, 2009 ; Zhang et al, 2014b ). We applied Hessian-SIM to image the subcellular localization of GFP-SRFBP1 at high spatial resolution and observed that SRFBP1 closely surrounded RPA43-labeled FCs, which is known to be a subcompartment harboring active rDNA repeats.…”

Section: Resultsmentioning

confidence: 99%

Real-time imaging of RNA polymerase I activity in living human cells

Liu

Wen

et al. 2022

Journal of Cell Biology

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RNA polymerase I (Pol I) synthesizes about 60% of cellular RNA by transcribing multiple copies of the ribosomal RNA gene (rDNA). The transcriptional activity of Pol I controls the level of ribosome biogenesis and cell growth. However, there is currently a lack of methods for monitoring Pol I activity in real time. Here, we develop LiveArt (live imaging-based analysis of rDNA transcription) to visualize and quantify the spatiotemporal dynamics of endogenous ribosomal RNA (rRNA) synthesis. LiveArt reveals mitotic silencing and reactivation of rDNA transcription, as well as the transcriptional kinetics of interphase rDNA. Using LiveArt, we identify SRFBP1 as a potential regulator of rRNA synthesis. We show that rDNA transcription occurs in bursts and can be altered by modulating burst duration and amplitude. Importantly, LiveArt is highly effective in the screening application for anticancer drugs targeting Pol I transcription. These approaches pave the way for a deeper understanding of the mechanisms underlying nucleolar functions.

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Section: Resultsmentioning

confidence: 99%

Real-time imaging of RNA polymerase I activity in living human cells

Liu

Wen

et al. 2022

Journal of Cell Biology

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“…These 71 genes included target genes for MSI with cancer-related functions (15 tumor suppressor-like genes and 16 oncogenes) and in which the frameshift mutated proteins may have retained complete or partial biological activity. Examples include the tumor suppressor genes WISP3 23 , PANK1 24 and SRFBP1 25 , and the oncogene JAK1 26 , 27 (Fig. 1c ).…”

Section: Resultsmentioning

confidence: 99%

Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability

et al. 2018

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Nonsense-mediated mRNA decay (NMD) is responsible for the degradation of mRNAs with a premature termination codon (PTC). The role of this system in cancer is still quite poorly understood. In the present study, we evaluated the functional consequences of NMD activity in a subgroup of colorectal cancers (CRC) characterized by high levels of mRNAs with a PTC due to widespread instability in microsatellite sequences (MSI). In comparison to microsatellite stable (MSS) CRC, MSI CRC expressed increased levels of two critical activators of the NMD system, UPF1/2 and SMG1/6/7. Suppression of NMD activity led to the re-expression of dozens of PTC mRNAs. Amongst these, several encoded mutant proteins with putative deleterious activity against MSI tumorigenesis (e.g., HSP110DE9 chaperone mutant). Inhibition of NMD in vivo using amlexanox reduced MSI tumor growth, but not that of MSS tumors. These results suggest that inhibition of the oncogenic activity of NMD may be an effective strategy for the personalized treatment of MSI CRC.

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“…The localization of p49/STRAP protein has been studied experimentally, either through transfection assays or proteomic analyses [1,13,19-21]. For instance, Lamond’s group has reported that p49/STRAP (SRFBP1) (ID # Q96DK2, or IPI00304493) is among a number of proteins, including Werner syndrome helicase, Bloom’s syndrome helicase and nucleolin, that are localized in the nucleolus [20,21].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of p49/STRAP alters cellular cytoskeletal structure and gross anatomy in mice

et al. 2014

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BackgroundThe protein p49/STRAP (SRFBP1) is a transcription cofactor of serum response factor (SRF) which regulates cytoskeletal and muscle-specific genes.ResultsTwo conserved domains were found in the p49/STRAP protein. The SRF-binding domain was at its N-terminus and was highly conserved among mammalian species, xenopus and zebrafish. A BUD22 domain was found at its C-terminus in three sequence databases. The BUD22 domain was conserved among mammalian p49/STRAP proteins, and yeast cellular morphogenesis proteins, which is involved in ribosome biogenesis that affects growth rate and cell size. The endogenous p49/SRAP protein was localized mainly in the nucleus but also widely distributed in the cytoplasm, and was in close proximity to the actin. Transfected GFP-p49/STRAP protein co-localized with nucleolin within the nucleolus. Overexpression of p49/STRAP reduced actin content in cultured cells and resulted in smaller cell size versus control cells. Increased expression of p49/STRAP in transgenic mice resulted in newborns with malformations, which included asymmetric abdominal and thoracic cavities, and substantial changes in cardiac morphology. p49/STRAP altered the expression of certain muscle-specific genes, including that of the SRF gene, which is a key regulator of cardiac genes at the developmental, structural and maintenance level and has two SRE binding sites.ConclusionsSince p49/STRAP is a co-factor of SRF, our data suggest that p49/STRAP likely regulates cell size and morphology through SRF target genes. The function of its BUD22 domain warrants further investigation. The observed increase in p49/STRAP expression during cellular aging may contribute to observed morphological changes in senescence.

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Interaction of Hsp70 with p49/STRAP, a serum response factor binding protein

Cited by 3 publications

References 28 publications

Real-time imaging of RNA polymerase I activity in living human cells

Real-time imaging of RNA polymerase I activity in living human cells

Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability

Overexpression of p49/STRAP alters cellular cytoskeletal structure and gross anatomy in mice

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