RETRACTED: Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11<sup>p58</sup> in mouse embryonic stem cells

Ohno, Satona; Shibayama, M.; Sato, Mitsuharu; Tokunaga, Akinori; Yoshida, Nobuaki

doi:10.4161/cc.10.21.17903

Cited by 24 publications

(29 citation statements)

References 39 publications

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“…As expected, depletion of PTBP1, hnRNP-K, and NCL abolished ESC colony formation (Figure 6C) and decreased the expression of pluripotency and neural precursor markers (Figures 6D-6F). The number of cells in these cultures was also reduced, consistent with the reported roles of PTBP1, hnRNP-K, and NCL in regulation of the cell cycle, proliferation, and cell death (Moumen et al, 2005; Ohno et al, 2011; Srivastava and Pollard, 1999). Furthermore, gene expression and bioinformatics analyses identified many common genes coregulated by TUNA and three associated RBPs (Figure 6G).…”

Section: Resultssupporting

confidence: 87%

“…Of note, there is evidence that NCL regulates the cell cycle, apoptosis, and maintenance of stemness in ESCs (Srivastava and Pollard, 1999; Yang et al, 2011). Finally, PTBP1 has been implicated in cell cycle regulation and neural differentiation, predominantly through post-transcriptional mechanisms (Ohno et al, 2011; Zheng et al, 2012). The diverse roles of these proteins suggest that the TUNA –RBP complex may regulate gene expression through multiple mechanisms.…”

Section: Resultsmentioning

confidence: 99%

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An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

et al. 2014

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SUMMARY Here, we generated the first genome-scale shRNA library targeting lincRNAs in the mouse. We performed an unbiased loss-of-function study in mouse embryonic stem cells (mESCs) and identified 20 novel lincRNAs involved in the maintenance of pluripotency. Among these, TUNA (Tcl1 Upstream Neuron-Associated lincRNA), was required for pluripotency and formed a complex with three RNA-binding proteins (RBPs). The TUNA–RBP complex was detected at the promoters of Nanog, Sox2, and Fgf4, and knockdown of TUNA or the individual RBPs inhibited neural differentiation of mESCs. TUNA showed striking evolutionary conservation of both sequence and central nervous system-restricted expression in vertebrates. Accordingly, knockdown of tuna in zebrafish caused impaired locomotor function, and TUNA expression in the brains of Huntington’s patients was significantly associated with disease grade. Our results suggest that the lincRNA TUNA plays a vital role in pluripotency and neural differentiation of ESCs and is associated with neurological function of adult vertebrates.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

et al. 2014

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“…To clarify this discrepancy, we performed a time-lapse imaging study. In embryonic stem cells, silencing PTBP1 causes a prolonged G 2 -M phase (49). Here, we found that silencing PTBP1 led to an increased G 2 -M population, based on time-lapse tracing of HCT116 cells.…”

Section: Discussionmentioning

confidence: 76%

“…As regarding CDK11 p58 expression levels, there is some discrepancy. Co-relationship between PTBP1, CDK11p58, and cell behavior is specifically dependent on cell types, for example, in ER-positive breast cancer, CDK11 p58 have negative effects on cancer progression (50), whereas in AR-independent prostate cancer, CDK11 p58 have a positive relationship to the cancer progression through sLZIP (51), and, in ES cells, the protein expression and IRES activity of CDK11 p58 in PTBP1 À/À ES cells is higher than that of wild-type ES cells, indicating that PTBP1 is involved in the repression of CDK11 p58 expression through IRES-dependent translation (49). However, our data indicate that PTBP1 have a positive effect on CKD11 p58 expression.…”

Section: Discussionmentioning

confidence: 99%

Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer

Takahashi

Nishimura

Kagawa

et al. 2015

Molecular Cancer Therapeutics

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Polypyrimidine tract-binding protein (PTBP1) is an RNAbinding protein with various molecular functions related to RNA metabolism and a major repressive regulator of alternative splicing, causing exon skipping in numerous alternatively spliced pre-mRNAs. Here, we have investigated the role of PTBP1 in colorectal cancer. PTBP1 expression levels were significantly overexpressed in cancerous tissues compared with corresponding normal mucosal tissues. We also observed that PTBP1 expression levels, c-MYC expression levels, and PKM2: PKM1 ratio were positively correlated in colorectal cancer specimens. Moreover, PTBP1 expression levels were positively correlated to poor prognosis and lymph node metastasis. In analyses of colorectal cancer cells using siRNA for PTBP1, we observed that PTBP1 affects cell invasion, which was partially correlated to CD44 splicing, and this correlation was also confirmed in clinical samples. PTBP1 expression also affected anchorage-independent growth in colorectal cancer cell lines. PTBP1 expression also affected cell proliferation. Using timelapse imaging analysis, PTBP1 was implicated in prolonged G 2 -M phase in HCT116 cells. As for the mechanism of prolonged G 2 -M phase in HCT116 siPTBP1 cells, Western blotting revealed that PTBP1 expression level was correlated to CDK11 p58 expression level, which was reported to play an important role on progression to complete mitosis. These findings indicated that PTBP1 is a potential therapeutic target for colorectal cancer.

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“…CDK11/p58 is a well-characterized endogenous mRNA that is only translated during mitosis by an IRES element (Cornelis et al 2000;Wilker et al 2007). Distinct ITAFs, including PTB ( polypyrimidine tract-binding protein) and UNR (upstream of N-RAS), have been shown to regulate CDK11/p58 expression (Tinton et al 2005;Ohno et al 2011). In the context of an oncogenic lesion such as Myc hyperactivation, an aberrant increase in cap-dependent translation specifically impairs the mitotic translational switch from cap-to IRES-dependent translation (Fig.…”

Section: Translational Control In Cancer Etiologymentioning

confidence: 99%

Translational Control in Cancer Etiology

Ruggero

2012

Cold Spring Harbor Perspectives in Biology

305

207

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The link between perturbations in translational control and cancer etiology is becoming a primary focus in cancer research. It has now been established that genetic alterations in several components of the translational apparatus underlie spontaneous cancers as well as an entire class of inherited syndromes known as "ribosomopathies" associated with increased cancer susceptibility. These discoveries have illuminated the importance of deregulations in translational control to very specific cellular processes that contribute to cancer etiology. In addition, a growing body of evidence supports the view that deregulation of translational control is a common mechanism by which diverse oncogenic pathways promote cellular transformation and tumor development. Indeed, activation of these key oncogenic pathways induces rapid and dramatic translational reprogramming both by increasing overall protein synthesis and by modulating specific mRNA networks. These translational changes promote cellular transformation, impacting almost every phase of tumor development. This paradigm represents a new frontier in the multihit model of cancer formation and offers significant promise for innovative cancer therapies. Current research, in conjunction with cutting edge technologies, will further enable us to explore novel mechanisms of translational control, functionally identify translationally controlled mRNA groups, and unravel their impact on cellular transformation and tumorigenesis.

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RETRACTED: Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11^p58 in mouse embryonic stem cells

Cited by 24 publications

References 39 publications

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer

Translational Control in Cancer Etiology

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RETRACTED: Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11p58 in mouse embryonic stem cells

Cited by 24 publications

References 39 publications

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

An Evolutionarily Conserved Long Noncoding RNA TUNA Controls Pluripotency and Neural Lineage Commitment

Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer

Translational Control in Cancer Etiology

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Product

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About

RETRACTED: Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11^p58 in mouse embryonic stem cells