Proliferation Potential-Related Protein, an Ideal Esophageal Cancer Antigen for Immunotherapy, Identified Using Complementary DNA Microarray Analysis

Yamada, Yoshitake; Nakatsura, Tetsuya; Monji, Mikio; Senju, Satoru; Matsuyoshi, Hidetake; Tsukamoto, Hirotake; Hosaka, Seiji; Kohno, Hiroyuki; Fukuma, Daiki; Ikuta, Yoshiaki; Katagiri, Toyomasa; Furukawa, Yoichi; Ito, Hiromi; Shinohara, Masanori; Nakamura, Yusuke; Nishimura, Yasuharu

doi:10.1158/1078-0432.ccr-04-0841

Cited by 60 publications

(70 citation statements)

References 41 publications

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“…Third, alteration of PACT expression and/or activity may be an important event during tumorigenesis. Consistent with this hypothesis, PACT is widely expressed in many tumor cell lines, and its expression is found to be increased in tumors, such as esophageal (10) and breast cancer (L.L., unpublished data). However, the correlation of PACT overexpression and tumorigenesis remains unclear.…”

Section: Discussionmentioning

confidence: 57%

“…It has been shown that PACT interacts with both p53 and Rb in vitro and in vivo (9). PACT is highly up-regulated in esophageal cancer and may be a promising target for immunotherapy (10). Stable overexpression of specific segments of the PACT restricts mitotic progression at prometaphase and promotes mitotic apoptosis and camptothecin-induced apoptosis (11)(12)(13).…”

mentioning

confidence: 99%

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PACT is a negative regulator of p53 and essential for cell growth and embryonic development

Deng²,

Xing³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The tumor suppressor p53 regulates cell cycle progression and apoptosis in response to various types of stress, whereas excess p53 activity creates unwanted effects. Tight regulation of p53 is essential for maintaining normal cell growth. p53-associated cellular protein-testes derived (PACT, also known as P2P-R, RBBP6) is a 250-kDa Ring finger-containing protein that can directly bind to p53. PACT is highly up-regulated in esophageal cancer and may be a promising target for immunotherapy. However, the physiological role of the PACT-p53 interaction remains largely unclear. Here, we demonstrate that the disruption of PACT in mice leads to early embryonic lethality before embryonic day 7.5 (E7.5), accompanied by an accumulation of p53 and widespread apoptosis. p53-null mutation partially rescues the lethality phenotype and prolonged survival to E11.5. Endogenous PACT can interact with Hdm2 and enhance Hdm2-mediated ubiquitination and degradation of p53 as a result of the increase of the p53-Hdm2 affinity. Consequently, PACT represses p53-dependent gene transcription. Knockdown of PACT significantly attenuates the p53-Hdm2 interaction, reduces p53 polyubiquitination, and enhances p53 accumulation, leading to both apoptosis and cell growth retardation. Taken together, our data demonstrate that the PACT-p53 interaction plays a critical role in embryonic development and tumorigenesis and identify PACT as a member of negative regulators of p53.apoptosis ͉ embryonic lethality ͉ ubiquitination

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Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 99%

PACT is a negative regulator of p53 and essential for cell growth and embryonic development

Deng²,

Xing³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…In fact, the complex domain composition of RBBP6 suggests that the protein plays roles in multiple cellular events, perhaps functioning to integrate such pathways with premRNA processing. Indeed, RBBP6 has been reported to have roles in cell proliferation (Gao et al 2002) and differentiation (Witte and Scott 1997;), and RBBP6 levels are increased in a number of tumors (Yoshitake et al 2004;Motadi et al 2011;Chen et al 2013). In contrast to the behavior of full-length RBBP6, also known as iso1, iso3 is down-regulated in several tumors (Mbita et al 2012).…”

Section: Discussionmentioning

confidence: 99%

RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3′ UTRs

Giammartino

Ogami

et al. 2014

Genes Dev.

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Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb-and p53-binding protein, is a component of this complex and functions in 39 processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (''domain with no name''), that is required for 39 processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 39 processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 39 untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 39 processing, especially of RNAs with AU-rich 39 UTRs.

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“…Although recent advancements such as microarray in addition to traditional molecular methods have been used for screening ESCC in order to find the important molecular alterations that ultimately result in ESCC [20][21][22], nevertheless, thus far target biomarkers applicable for the detection and therapeutic strategies and genes to act as molecular targets have not been well identified, indicating further limitations in the effective treatment of ESCC. The high throughput and sensitive proteomic technology is hoped to open an effective venue for screening the novel cancer specific biomarkers for ESCC.…”

Section: Proteomics Of Esophageal Carcinomamentioning

confidence: 99%

Proteomics and Esophageal Cancer

Moghanibashi¹,

Zare²,

Jazii³

2012

Esophageal Cancer - Cell and Molecular Biology, Biomarkers, Nutrition and Treatment

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Proliferation Potential-Related Protein, an Ideal Esophageal Cancer Antigen for Immunotherapy, Identified Using Complementary DNA Microarray Analysis

Cited by 60 publications

References 41 publications

PACT is a negative regulator of p53 and essential for cell growth and embryonic development

PACT is a negative regulator of p53 and essential for cell growth and embryonic development

RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3′ UTRs

Proteomics and Esophageal Cancer

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