Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins

Ivanova, Alla V.; Ivanov, Sergey V.; Lerman, M. L.

doi:10.1007/s00018-004-4423-2

Cited by 36 publications

(26 citation statements)

References 63 publications

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“…These results highlight the critical importance of the STRA13 C-terminus for the transcriptional repression. As the STRA13 C-terminal region was previously associated with protein-protein interaction (Sun and Taneja, 2000;Ivanova et al, 2004Ivanova et al, , 2005, the obtained data suggested a cooperation between STRA13 and other transcriptional regulator(s) on the STAT1 promoter.…”

Section: Stra13 Represses the Stat1 Promoter Independently Of E-boxesmentioning

confidence: 52%

“…For Western blot, cells were lysed in RIPA buffer and proteins fractionated as described earlier (Ivanova et al, 2004). STRA13 antibodies against the endogenous protein were ordered from Washington Biotechnology (Washington, DC) and validated in our previous study (Ivanova et al, 2005). STAT1 and STAT3 antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).…”

Section: Northern and Western Blot Analysesmentioning

confidence: 99%

“…STRA13 is expressed in differentiating embryonic and adult tissues (Boudjelal et al, 1997;Shen et al, 1997), responds to a broad range of growth stimuli (Shen et al, 2001;Zawel et al, 2002), and serves as a key regulator of lymphoid cell development and activation (Sun et al, 2001;Seimiya et al, 2004). Transcriptional repression activity of STRA13 can be established through direct DNA binding to the E-box (St-Pierre et al, 2002;Zawel et al, 2002;Azmi et al, 2003) via its basic region, or through indirect involvement in transcriptional modulation via interaction with multiple transcription factors, such as USF (Dhar and Taneja, 2001), TBP and TFIIB (Boudjelal et al, 1997), MyoD (Azmi et al, 2003), and MSP58 (Ivanova et al, 2005), or with the HDAC complex components (Sun and Taneja, 2000). Recently, our data on the interaction of STRA13 with STAT3 (Ivanova et al, 2004) implicated STRA13 in the JAK/STAT signal transduction pathway that plays a central role in regulation of the immune system (Bach et al, 1997;Shuai and Liu, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13

et al. 2006

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DEC1/STRA13 is a bHLH type transcriptional regulator involved with immune regulation, hypoxia response and carcinogenesis. We recently demonstrated that STRA13 interacts with STAT3 in the transcriptional activation of STAT-dependent promoters. Here, we pursue STRA13 involvement in the JAK/STAT pathway by studying its role in STAT1 expression. First, we showed that VHL deficiency or HIF-1 activation resulted in the repression of endogenous STAT1 mediated by STRA13. We then characterized the STAT1 proximal promoter to assess its response to STRA13 by transient coexpression in a luciferase reporter assay. Using sequential truncation and site-directed mutagenesis of the STAT1 promoter with STRA13 deletion constructs, we showed that the STRA13 C-terminal trans-activation domain, which is known to bind HDAC1, mostly determines the repressive activity. Involvement of HDAC activity in STAT1 regulation was validated by TSA inhibition and chromatin immunoprecipitation (ChIP) assay. Thus, we demonstrate that STRA13-mediated repression of STAT1 transcription utilizes an HDAC1-dependent mechanism. Furthermore, we show that targets of unphosphorylated STAT1, such as antigen presenting genes and CASP1, are also repressed by hypoxia possibly through the same STRA13-mediated mechanism. Thus, the newly discovered link between HIF-1 and STAT1 reveals a previously unknown role of STRA13 in hypoxia and carcinogenesis. Oncogene Shuai and Liu, 2003). STAT1 and STAT3 are that two principal signal transducers in this pathway that serve disparate physiological roles through transcriptional activation of different targets (Qing and Stark, 2004). In carcinogenesis, these proteins have opposite effects on cell growth and survival; while STAT3 is an oncogene (Bromberg et al., 1999), STAT1 possesses tumor suppressor properties (Kaplan et al., 1998;Bromberg and Darnell, 2000). STAT1's major functions, executed through the IFNg-induced Y701 phosphorylation, are inhibition of proliferation, activation of antimicrobial and antiviral responses, and induction of antitumor immune defense (Shuai et al., 1996;Kaplan et al., 1998;Stark et al., 1998). Recent data suggest that unphosphorylated STAT1 may also play an important role in the regulation of constitutive expression of certain genes (Kumar et al., 1997;Chatterjee-Kishore et al., 2000;Meyer et al., 2002).In this study, we identify STAT1 as a transcriptional target of STRA13, investigate the molecular mechanisms of STRA13 activity on the STAT1 promoter, and assess the downstream effects of this activity. Results Introduction of VHL in clear cell carcinoma cells stimulates STAT1 expressionOur previous study revealed functional interaction between a VHL/HIF-1 target STRA13 and STAT3 (Ivanova et al., 2004). To find out if STRA13 can be associated with other constituents of the JAK/STAT pathway, we took advantage of cell lines with different VHL status. The original clear cell carcinoma cell lines UM-RC-6 and 786-0 contain frameshift mutations in the remaining VHL allele that make aberrant proteins...

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Section: Stra13 Represses the Stat1 Promoter Independently Of E-boxesmentioning

confidence: 52%

Section: Northern and Western Blot Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13

et al. 2006

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“…In addition, the C terminus of PTEN has been shown to bind to the nucleolar 58-kDa microspherule protein (MSP58), which forms a complex with the hypoxia-inducible transcription factor DEC1 (differentiated embryo-chondrocyte expressed gene 1) implicated in the pVHL-HIF pathway under chronic hypoxia. [36][37][38] It is worth investigating whether these potential binding partners interact with PTEN in EBs and whether they are involved in PHD2 and HIF-2α regulation.…”

Section: Discussionmentioning

confidence: 99%

PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation during epithelial lumen formation

Liu

Saadat

et al. 2014

Cell Death Differ

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The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia-and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3.

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“…Additional studies showed that, in the nucleus, MSP58 could function to regulate transcription through its interactions with the transcription factors Daxx, STRA13, and the RNA-binding protein FMR (Lin et al, 2002;Ivanova et al, 2005;Davidovic et al, 2006). A study showed that TOJ3, the quail homologue of MSP58, displayed transformation activity in juntransformed fibroblasts (Bader et al, 2001), whereas the tumor suppressor gene PTEN could suppress its transforming activity (Okumura et al, 2005).…”

mentioning

confidence: 99%

MSP58 Knockdown Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

Zheng²,

Zhang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression.

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Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins

Cited by 36 publications

References 63 publications

Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13

Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13

PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation during epithelial lumen formation

MSP58 Knockdown Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

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