Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbp(pc-/-);Pten(pc+/-) mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp(-/-); Pten(+/-) and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27(KIP1), and p21(CIP1). Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbp(pc-/-);Pten(pc+/-) mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic-targeted therapy in patients with prostate cancer.
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PMID:CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy. 2449 99

Root branching or lateral root formation is crucial to maximize a root system acquiring nutrients and water from soil. A lateral root (LR) arises from asymmetric cell division of founder cells (FCs) in a pre-branch site of the primary root, and FC establishment is essential for lateral root formation. FCs are known to be specified from xylem pole pericycle cells, but the molecular genetic mechanisms underlying FC establishment are unclear. Here, we report that, in Arabidopsis thaliana, a PRC2 (for Polycomb repressive complex 2) histone H3 lysine-27 (H3K27) methyltransferase complex, functions to inhibit FC establishment during LR initiation. We found that functional loss of the PRC2 subunits EMF2 (for EMBRYONIC FLOWER 2) or CLF (for CURLY LEAF) leads to a great increase in the number of LRs formed in the primary root. The CLF H3K27 methyltransferase binds to chromatin of the auxin efflux carrier gene PIN FORMED 1 (PIN1), deposits the repressive mark H3K27me3 to repress its expression, and functions to down-regulate auxin maxima in root tissues and inhibit FC establishment. Our findings collectively suggest that EMF2-CLF PRC2 acts to down-regulate root auxin maxima and show that this complex represses LR formation in Arabidopsis.
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PMID:A histone H3 lysine-27 methyltransferase complex represses lateral root formation in Arabidopsis thaliana. 2471 Dec 89

Nicotinamide N -methyltransferase (NNMT) has been identified to be associated with tumorigenesis and the malignant transformation of numerous types of cancer. The aim of the present study was to explore the expression and prognostic significance of NNMT in prostate cancer (PCa). Immunohistochemical NNMT expression was examined in 26 cases of benign prostate hyperplasia (BPH), 18 cases of high-grade prostatic intraepithelial neoplasia (HGPIN) and 120 cases of PCa. While rarely expressed in BPH (8/26 cases; 30.8%), NNMT was found to be significantly upregulated in HGPIN (15/18 cases; 83.3%) and PCa (77/120 cases; 64.2%). Clinicopathological analysis revealed that NNMT expression was negatively correlated with Gleason score (P<0.001). Furthermore, Kaplan-Meier survival curves revealed that high NNMT expression was associated with prolonged progression-free survival (PFS) and overall survival (OS) times in patients with advanced PCa. Multivariate analysis showed that NNMT was an independent prognostic marker of PFS and OS in patients with advanced PCa. The results of the present study suggested that NNMT may contribute to the development of PCa and may potentially be a favorable prognostic marker for the survival of patients with advanced PCa.
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PMID:Nicotinamide N-methyltransferase is overexpressed in prostate cancer and correlates with prolonged progression-free and overall survival times. 2512 Jun 81

The H3K27 methyltransferase CLF inhibits lateral root (LR) formation through depositing the repressive H3K27me3 mark to the chromatin of PIN1, a key polar auxin transporter gene. Here, we show that the H3K27me3 demethylase REF6 promotes lateral root primordium initiation and LR emergence. REF6 directly binds to the chromatin of PIN1/3/7. Dysfunction in REF6 results in increased levels of H3K27me3 on PIN1/3/7 and suppressed expression of PIN genes. Genetic analysis of the clf ref6 double mutant revealed an antagonistic action between CLF and REF6, in terms of LR formation. Our findings indicate that H3K27 methylation and demethylation activities are likely coordinated to ensure proper LR organogenesis.
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PMID:REF6 promotes lateral root formation through de-repression of PIN1/3/7 genes. 3026 71

Ribosome production is an essential cellular process involving a plethora of trans-acting factors, such as nucleases, methyltransferases, RNA helicases and kinases that catalyse key maturation steps. Precise temporal and spatial regulation of such enzymes is essential to ensure accurate and efficient subunit assembly. Here, we focus on the maturation of the 3' end of the 18S rRNA in human cells. We reveal that human RIO2 is an active kinase that phosphorylates both itself and the rRNA methyltransferase DIM1 in vitro. In contrast to yeast, our data confirm that human DIM1 predominantly acts in the nucleus and we further demonstrate that the 21S pre-rRNA is the main target for DIM1-catalysed methylation. We show that the PIN domain of the endonuclease NOB1 is required for site 3 cleavage, while the zinc ribbon domain is essential for pre-40S recruitment. Furthermore, we also demonstrate that NOB1, PNO1 and DIM1 bind to a region of the pre-rRNA encompassing the 3' end of 18S and the start of ITS1, in vitro. Interestingly, NOB1 is present in the cell at higher levels than other pre-40S factors. We provide evidence that NOB1 is multimeric within the cell and show that NOB1 multimerisation is lost when ribosome biogenesis is blocked. Taken together, our data indicate a dynamic interplay of key factors associated with the 3' end of the 18S rRNA during human pre-40S biogenesis and highlight potential mechanisms by which this process can be regulated.
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PMID:Interactions and activities of factors involved in the late stages of human 18S rRNA maturation. 3063 16