Ribosomal protein S27L is a direct p53 target that regulates apoptosis

He, Haixiang; Sun, Yi

doi:10.1038/sj.onc.1210073

Cited by 97 publications

(96 citation statements)

References 32 publications

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“…While this manuscript was in preparation, He et al reported a similar finding indicating RPS27L as a novel p53 target that regulates apoptosis upon DNA damage (41). However, the data contrast with our findings, showing that RPS27L function as a proapoptotic molecule that mediates p53-induced apoptosis in etoposide (VP16)-treated HCT116 cells.…”

Section: Discussioncontrasting

confidence: 93%

Ribosomal Protein S27-like, a p53-Inducible Modulator of Cell Fate in Response to Genotoxic Stress

Tan²,

Li³

et al. 2007

Cancer Research

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Activation of the p53 tumor suppressor upon DNA damage elicits either cell cycle arrest or apoptosis, and the precise mechanism governing cell fate after p53 response has not been well defined. Through genomic analysis, we have identified the ribosomal protein S27-like (RPS27L) as a novel p53 transcriptional target gene. Although RPS27L mRNA levels were consistently induced after diverse p53 activating signals, its change in protein level was stimuli-dependent: it was up-regulated when cells were arrested in response to DNA-damaging agents Adriamycin or VP16 but was downregulated when cells underwent apoptosis in response to antimetabolite agent 5-fluorouracil. RPS27L is a nuclear protein that forms nuclear foci upon DNA damage. Depletion of RPS27L resulted in deficiency in DNA damage checkpoints, leading to conversion of DNA damage-induced p53 response from cell cycle arrest to apoptosis. We further show that RPS27L positively regulates p21 protein expression. Through this mechanism, RPS27L induction by p53 facilitates p21-mediated cell cycle arrest and protects against DNA damageinduced apoptosis. Thus, RPS27L modulates DNA damage response and functions as a part of the control switch to determine cell fate to DNA damage-p53 response. [Cancer Res

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Section: Discussioncontrasting

confidence: 93%

Ribosomal Protein S27-like, a p53-Inducible Modulator of Cell Fate in Response to Genotoxic Stress

Tan²,

Li³

et al. 2007

Cancer Research

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“…Several of these genes are important in tumorigenesis, including RPS27L and INHBC, which play important roles in p53 regulation and oncogenic transformation. 20,33 Nevertheless, when subset #16 cases were pooled with non-subset 4/16 cases, the observed gene expression differences between subset #4 haematologica | 2010; 95(12) Figure 2. Visualization of differentially expressed genes using hierarchical clustering of genes in subset #4 versus all other cases.…”

Section: Discussionmentioning

confidence: 99%

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Marincevic¹,

Mansouri²,

Kanduri³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundNumerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with "stereotyped" B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level. Design and MethodsWe investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays. ResultsAlthough generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients. ConclusionsOur novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.Key words: stereotyped BCR, IGHV4-34, chronic lymphocytic leukemia, gene expression. IGHV4-34 B-cell receptors. Haematologica 2010;95(12):2072-2079. doi:10.3324/haematol.2010 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Citation: Marincevic M, Mansouri M, Kanduri M, Isaksson A, Göransson H, Smedby KE, Jurlander J, Juliusson G, Davi F, Stamatopoulos K, and Rosenquist R. Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

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“…Unlike hematologic malignancies, this aberration was only rarely documented by CGH in a few types of sarcomas, such as gastrointestinal intestinal tumors (33), endometrial stromal sarcomas (34), and osteosarcomas (35 (38,40,41), whereas RPS27L, encoding a novel ribosomal protein, may represent another candidate (36). More intriguingly, sequences in the intron 1 region of both genes can be bound by P53 to mediate its proapoptotic and/or antiproliferative functions upon cellular stresses (36,40,41). In this context, we postulate a model wherein oncogenic signaling abnormality (e.g., COL6A3-CSF1 gene fusion) may initially drive the development of benign D-TSGCT and elicit cellular responses mediated by wild-type P53.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and Biogenetic Features of Diffuse-Type Tenosynovial Giant Cell Tumors: The Potential Roles of Cyclin A, P53, and Deletion of 15q in Sarcomatous Transformation

Huang

West

Tzeng

et al. 2008

Clinical Cancer Research

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Purpose: Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an aggressive proliferation of synovial-like mononuclear cells with inflammatory infiltrates. Despite the COL6A3-CSF1 gene fusion discovered in benign lesions, molecular aberrations of malignant D-TSGCTs remain unidentified. Experimental Design: We used fluorescent in situ hybridization and in situ hybridization to evaluate CSF1 translocation and mRNA expression in six malignant D-TSGCTs, which were further immunohistochemically compared with 24 benign cases for cell cycle regulators involving G 1 phase and G 1 -S transition. Comparative genomic hybridization, real-time reverse transcription-PCR, and a combination of laser microdissection and sequencing were adopted to assess chromosomal imbalances, cyclin A expression, and TP53 gene, respectively. Results: Five of six malignant D-TSGCTs displayed CSF1 mRNA expression by in situ hybridization, despite only one having CSF1translocation. Cyclin A (P = 0.008) and P53 (P < 0.001) could distinguish malignant from benign lesions without overlaps in labeling indices. Cyclin A transcripts were more abundant in malignant D-TSGCTs (P < 0.001). All malignant cases revealed a wild-type TP53 gene, which was validated by an antibody specifically against wild-type P53 protein.Chromosomal imbalances were only detected in malignant D-TSGCTs, with DNA losses predominating over gains. Notably, -15q was recurrently identified in five malignant D-TSGCTs, four of which showed a minimal overlapping deletion at 15q22-24. Conclusions: Deregulated CFS1 overexpression is frequent in malignant D-TSGCTs. The sarcomatous transformation involves aberrations of cyclin A, P53, and chromosome arm 15q. Cyclin A mRNA is up-regulated in malignant D-TSGCTs. Non^random losses at 15q22-24 suggest candidate tumor suppressor gene(s) in this region. However, P53 overexpression is likely caused by alternative mechanisms rather than mutations in hotspot exons.Tenosynovial giant cell tumors (TSGCT) are unique mesenchymal lesions that arise from the synovial lining of articular spaces, bursal sacs, and tendon sheaths (1, 2). The neoplastic property of TSGCTs has been supported by the identification of DNA aneuploidy and clonal karyotypic aberrations in these tumors, such as trisomies 7 and 5 and/or translocations involving chromosomal regions 1p11-13, 2q35-37, or 16q22-24 (2 -6). Given the difference in clinical behavior, TSGCTs are further divided by growth patterns into localized and diffuse types and by the predominant location of occurrence into extra-articular and intra-articular forms (1 -4). Histologically, diffuse-type TSGCT (D-TSGCT), i.e., pigmented villonodular synovitis if located intra-articularly, is an infiltrative proliferation of synovial-like mononuclear cells accompanied by heterogeneous inflammatory infiltrates among varying degrees of collagenous stroma (1, 2, 7). It frequently develops multiple local recurrences that are sometimes difficult to control by surgical excision and can severely compromise joint function...

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Ribosomal protein S27L is a direct p53 target that regulates apoptosis

Cited by 97 publications

References 32 publications

Ribosomal Protein S27-like, a p53-Inducible Modulator of Cell Fate in Response to Genotoxic Stress

Ribosomal Protein S27-like, a p53-Inducible Modulator of Cell Fate in Response to Genotoxic Stress

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Immunohistochemical and Biogenetic Features of Diffuse-Type Tenosynovial Giant Cell Tumors: The Potential Roles of Cyclin A, P53, and Deletion of 15q in Sarcomatous Transformation

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