The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

Moniaux, Nicolas; Némos, Christophe; Schmied, Bruno M.; Chauhan, Subhash C.; Deb, Sanjukta; Morikane, Keita; Choudhury, Amit; VanLith, Michelle L.; Sutherlin, Marie E.; Sikela, James M.; Hollingsworth, Michael A.; Batra, Surinder K.

doi:10.1038/sj.onc.1209353

Cited by 73 publications

(81 citation statements)

References 43 publications

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“…We found that PD2/hPaf1, is overexpressed in the poorly differentiated pancreatic cancer cell line, Panc1. Further, the targeted overexpression of this gene in the NIH3T3 cell line led to transformation of the cells (Moniaux et al, 2006). These results suggest that the PD2/hPaf1 gene is a potential candidate of the oncogene family.…”

Section: Pd2/hpaf1 Is a New Candidate Oncogenementioning

confidence: 67%

“…These proteins are found to be associated with cancer progression either by overexpression or by downregulation during the course of the disease. We have reported a new candidate oncogene, pancreatic differentiation 2 (PD2)/hPaf1, a member of the hPAF complex, which is dysregulated in cancer (Moniaux et al, 2006). Another component of the hPAF complex with a known role in cancer is the hCdc73 subunit, also called parafibromin (Zhang et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Human RNA polymerase II-associated factor complex: dysregulation in cancer

et al. 2007

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Genetic instabilities are believed to be one of the major causes of developing a cancer phenotype in humans. During the progression of cancer, aberrant expression of proteins, either owing to genetic (amplification, mutation and deletion) or epigenetic modifications (DNA methylation and histone deacetylation), contributes in different ways to the development of cancer. By differential screening analysis, an amplification of the 19q13 locus containing a novel pancreatic differentiation 2 (PD2) gene was identified. PD2 is the human homolog of the yeast RNA polymerase II-associated factor 1 (yPaf1) and is part of the human RNA polymerase II-associated factor (hPAF) complex. hPAF is comprised of five subunits that include PD2/hPaf1, parafibromin, hLeo1, hCtr9 and hSki8. This multifaceted complex was first identified in yeast (yPAF) and subsequently in Drosophila and human. Recent advances in the study on PAF have revealed various functions of the complex in human, which are similar to yPAF, including efficient transcription elongation, mRNA quality control and cell-cycle regulation. Although the precise function of this complex in cancer is not clearly known, some of its subunits have been linked to a malignant phenotype. Its core subunit, PD2/hPaf1, is amplified and overexpressed in many cancers. Further, an overexpression of PD2/hPaf1 results in the induction of a transformed phenotype, suggesting its possible involvement in tumorigenesis. The parafibromin subunit of the hPAF complex is a product of the HRPT-2 (hereditary hyperparathyroidism type 2) tumor suppressor gene, which is mutated in the germ line of hyperparathyroidismjaw tumor patients. This review focuses on the functions of the PAF complex and its individual subunits, the interaction of the subunits with each other and/or with other molecules, and dysregulation of the complex, providing an insight into its potential involvement in the development of cancer.

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Section: Pd2/hpaf1 Is a New Candidate Oncogenementioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Human RNA polymerase II-associated factor complex: dysregulation in cancer

et al. 2007

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“…For example, PAF1 is amplified in pancreatic cancer, leading to the overexpression of Paf1 protein in poorly differentiated pancreatic cancer cells (Moniaux et al 2006). The overexpressed Paf1 regulates self-renewal and drug resistance of pancreatic and ovarian cancer stem cells (Vaz et al 2014).…”

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confidence: 99%

Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis

Zeng

2015

Genes Dev.

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The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold subunit in hPAFc, is highly expressed in estrogen receptor α-positive (ERα + ) luminal breast cancer, and the high expression of Ctr9 correlates with poor prognosis. Knockdown of Ctr9 in ERα + breast cancer cells almost completely erased estrogen-regulated transcriptional response. At the molecular level, Ctr9 enhances ERα protein stability, promotes recruitment of ERα and RNAPII, and stimulates transcription elongation and transcription-coupled histone modifications. Knockdown of Ctr9, but not other hPAFc subunits, alters the morphology, proliferative capacity, and tamoxifen sensitivity of ERα + breast cancer cells. Together, our study reveals that Ctr9, a key subunit of hPAFc, is a central regulator of estrogen signaling that drives ERα + breast tumorigenesis, rendering it a potential target for the treatment of ERα + breast cancer.

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“…The yeast Paf1 complex is also known to participate in cell cycle control (Porter et al, 2002). Interestingly, it was reported that hPaf1 overexpression resulted in an enhancement of cell proliferation in opposition to the tumor suppressor activity of PF (Moniaux et al, 2006). Thus, overexpression of PF or hPaf1 affects the regulation of cell growth.…”

Section: Discussionmentioning

confidence: 99%

Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen

et al. 2007

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Parafibromin (PF) is a 531-amino acid protein encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal-dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of PF's overexpression on cell proliferation, we performed assays in four different cell lines. The transient overexpression of PF inhibited cell growth in HEK293 and NIH3T3 cells, but enhanced cell growth in the SV40 large T antigen-expressing cell lines such as 293FT and COS7 cells. In 293FT cells, PF was found to interact with SV40 large T antigen and its overexpression promoted entry into the S phase, implying that the interaction enhanced progression through the cell cycle. The tumor suppressor protein PF acts as a positive regulator of cell growth similar to an oncoprotein in the presence of SV40 large T antigen.

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The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

Cited by 73 publications

References 43 publications

Human RNA polymerase II-associated factor complex: dysregulation in cancer

Human RNA polymerase II-associated factor complex: dysregulation in cancer

Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis

Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen

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