Cloning of a novel human RNA polymerase II subunit downregulated by doxorubicin: new potential mechanisms of drug related toxicity

Fanciulli, Maurizio; Bruno, Tiziana; Cerboni, Cristina; Bonetto, Francesco; Iacobini, Carla; Frati, Luigi; Piccoli, Mario; Floridi, Aristide; Santoni, A.; Punturieri, Antonello

doi:10.1016/0014-5793(96)00277-3

Cited by 23 publications

(43 citation statements)

References 18 publications

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“…The rabbit polyclonal antibodies against human RPB11 and RPB3 have been described previously (Fanciulli et al, 1996;Corbi et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

“…We found that RPB11 and RPB3 are expressed at high levels in adult human skeletal muscle and heart (Fanciulli et al, 1996;Fanciulli et al, 1998), and that RPB3 expression is regulated during murine C2C7 myoblast differentiation (Corbi et al, 2002). In addition, the involvement of RPB3 in tissue-specific transcription was demonstrated by its direct contact with transcription factors including ATF4 (a member of the ATF/CREB family) and Myogenin (a member of the MyoD gene family) (De Angelis et al, 2003;Corbi et al, 2002).…”

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confidence: 90%

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RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

Corbi

Bruno

Angelis

et al. 2005

Journal of Cell Science

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Here, we show that the subcellular localization of α-like RNA polymerase II core subunit 3 (RPB3) is regulated during muscle differentiation. We have recently demonstrated that the expression of RPB3 is regulated during muscle differentiation and that, inside RNA polymerase II (RNAP II), it is directly involved in contacting regulatory proteins such as the myogenic transcription factor Myogenin and activating transcription factor ATF4. We show for the first time, that RPB3, in addition to its presence and role inside the RNAP II core enzyme, accumulates in the cytoplasm of cycling myogenic cells and migrates to the nucleus upon induction of the differentiation program. Furthermore, using human RPB3 as bait in a yeast two-hybrid system, we have isolated a novel RPB3 cytoplasmic interacting protein, HCR. HCR, previously identified as α-helix coiled-coil rod homologue, is one of the psoriasis vulgaris (PV) candidate genes. In cycling myogenic C2C7 cells, we show that the RPB3 protein directly interacts with HCR within the cytoplasm. Finally, knocking down HCR expression by RNA interference, we demonstrate that HCR acts as cytoplasmic docking site for RPB3.

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“…The rabbit polyclonal antibodies against human RPB11 and RPB3 have been described previously (Fanciulli et al, 1996;Corbi et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 90%

RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

Corbi

Bruno

Angelis

et al. 2005

Journal of Cell Science

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“…As determined by gene ontology analysis, our radiation-induced 30 gene signature was significantly enriched for genes involved in pyruvate metabolism, generation of precursor metabolites and energy, suggesting that tumors most sensitive to chemotherapy are those with highest metabolic activity, consistent with the known mechanisms of action of several chemotherapeutics used in the datasets we analyzed, including doxorubicin and capecitabine (47)(48)(49)(50)(51)(52)(53). Genes composing our 30 gene signature include lactate dehydrogenase B (LDHB), which is a subunit of the lactate dehydrogenase enzyme, the key glycolytic enzyme catalyzing formation of lactic acid from pyruvate.…”

Section: Discussionmentioning

confidence: 58%

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Chao

Balletta

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

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The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. In this study, we hypothesized that due to similarities between radiation-and chemotherapy-induced cellular response mechanisms, radiation-responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiationresponsive genes across subtypes. These murine tumor radiation-induced genes were then converted to their human orthologs, and subsequently tested as a predictor of pathologic complete response (pCR), which was validated on two independent published neoadjuvant chemotherapy datasets of genomic data with chemotherapy response. A radiation-induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples on two independent published datasets and was found to be significantly predictive of pCR. Multivariate logistic regression analysis in both independent datasets showed 1 Address for correspondence: Leo W. Jenkins Cancer Center, The Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Greenville, NC 27834; oh.daniel.s@gmail.com. Supplementary Fig. S1. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster A shown Fig. 3 (upper left) significantly enriched for genes involved in wound and inflammatory response as determined by DAVID. Supplementary Fig. S2. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster B from Fig. 3 (upper left) significantly enriched for genes involved in M phase, mitotic cell cycle and ribosome as determined by DAVID. Supplementary Fig. S3. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster C from Fig. 3 (upper left) significantly enriched for genes involved in muscle contraction, muscle cell development, and myofibril assembly as determined by DAVID. Supplementary Fig. S4. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster D from Fig. 3 (upper left) significantly enriched for genes involved in positive regulation of mesenchymal cell proliferation, blood vessel development and cell motion as determined by DAVID. Supplementary Fig. S5. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster E from Fig. 3 (upper left) significantly enriched for genes involved in zinc ion and DNA binding as determined by DAVID. SUPPLEMENTARY INFORMATION HHS Public Access

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“…The major disadvantage, however, is that increased physical protection is required. 33 P is a viable alternative because it combines the advantages of both 35 S and 32 P and is more sensitive (139). A 1-Ci portion of 33 P allows the same sensitivity and resolution as 5 Ci of 35 S, thus making it cost-effective (76).…”

Section: Modificationsmentioning

confidence: 99%

“…The potential applications in medical mycology are readily apparent. One approach is to treat sensitive and resistant cells with a drug and then analyze them by DDRT-PCR (33). The difference between resistant and sensitive cells may also be analyzed in the absence of drug in order to provide insight into why a cell is sensitive or resistant to drug action (72).…”

Section: Drug Resistance and Targets For Drugsmentioning

confidence: 99%

Applications of Differential-Display Reverse Transcription-PCR to Molecular Pathogenesis and Medical Mycology

Sturtevant

2000

Clinical Microbiology Reviews

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Cloning of a novel human RNA polymerase II subunit downregulated by doxorubicin: new potential mechanisms of drug related toxicity

Cited by 23 publications

References 18 publications

RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Applications of Differential-Display Reverse Transcription-PCR to Molecular Pathogenesis and Medical Mycology

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