LincRNA-p21
lincRNA-p21, a p53-activated key regulator of the protein signalling pathways underlying carcinogenesis.
Contents
Annotation
Name
lincRNA-p21 (HGNC:43652)
Alias
TP53COR1: tumor protein p53 pathway co-repressor 1 (HGNC:43652) linc-p21 (HGNC:43652)
Previous names
tumor protein p53 pathway corepressor 1 (non-protein coding) (HGNC:43652)
Characteristics
lincRNA-p21 is a large intergenic non-coding RNA induced by p53. Its chromosomal location is at 6p21.2 and it resides ∼15Kb upstream of the gene encoding the critical cell cycle regulator Cdkn1a (also known as p21), a canonical transcriptional target of p53 [2]. Full-length transcriptional unit of lincRNA-p21 contains two exons comprising 3.1Kb. lincRNA-p21 is transcribed in the opposite orientation from the Cdkn1a gene. It bears consensus p53 motif, which is bound by p53 and serves as a repressor in p53-dependent transcriptional responses. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with with heterogenous nuclear ribonucleoprotein K (hnRNP-K). This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis [1].
Function
lincRNA-p21- serves as a transcriptional repressor in the p53 pathway and plays a role in triggering apoptosis. LincRNA-p21 is associated with heterogenous nuclear ribonucleoprotein K (hnRNP-K )and localises this protein to promoters of genes, downregulated in the canonical p53 pathway and p53-mediated apoptosis, to maintain gene repression thus lincRNA-p21 may play an important role in tumour suppression by operating as a transcriptional repressor [2].
Regulation
lincRNA-p21 contains binding sites for the tumour suppressor p53 in its promoter and is directly activated by p53 in response to DNA damage [2].
Expression
LincRNA-p21 is expressed in both human and mouse cell-based systems by p53-dependent activation. siRNA-mediated inhibition of lincRNA-p21 affects the expression of hundreds of gene targets that are enriched for genes normally repressed by p53. Strikingly, the vast majority of these common target genes are derepressed upon inhibition of either p53 or lincRNA-p21 – suggesting that lincRNA-p21 functions as a downstream repressor in the p53 transcriptional response [1].
Diseases
Labs Working
- University of Queensland Diamantina Institute, R-Wing, Princess Alexandra Hospital, Ipswich Road, Wolloongabba, QLD 4102, Australia
- Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
- The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- Department of Cardiology, Chongqing Institute of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.
- Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA
- Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing, 210009, China.
- Laboratory of Cancer Research, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing, 210009, China.
- Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Core Facility Genomics and Proteomics, Bioinformatics Group, DKFZ, Heidelberg, Germany
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
References
- ↑ 1.0 1.1 1.2 Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response[J]. Cell. 2010, 142(3):409-419.
- ↑ 2.0 2.1 2.2 2.3 Cheetham SW, Gruhl F, Mattick JS & Dinger ME. Long noncoding RNAs and the genetics of cancer[J]. British journal of cancer. 2013, 108(12):2419-2425.
- ↑ Wu G, Cai J, Han Y, Chen J, Huang Z-P, Chen C et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity[J]. Circulation. 2014, 130(17):1452-1465.
- ↑ Peng W, Wu J & Feng J. LincRNA-p21 predicts favorable clinical outcome and impairs tumorigenesis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy[J]. Clinical and experimental medicine. 2017, 17(1):1-8.
- ↑ Blume CJ, Hotz-Wagenblatt A, Hüllein J, Sellner L, Jethwa A, Stolz T et al. p53-dependent non-coding RNA networks in chronic lymphocytic leukemia[J]. Leukemia. 2015, 29(10).
