Affinage

RPP14

Ribonuclease P protein subunit p14 · UniProt O95059

Length
124 aa
Mass
13.7 kDa
Annotated
2026-04-28
100 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPP14 is a protein subunit of human ribonuclease P (RNase P), directly associating with the catalytically active holoenzyme complex in HeLa cells (PMID:10024167). Beyond its structural role in RNase P, RPP14 together with its binding partner OIP2 possesses an intrinsic 3′→5′ phosphorolytic exoribonuclease activity that processes the 3′ terminus of precursor tRNA, an activity distinct from the endonucleolytic cleavage carried out by the RNase P core (PMID:11929972).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1999 High

    Establishing RPP14 as a bona fide RNase P subunit resolved its identity among the protein components of the human holoenzyme, showing it physically associates with a catalytically active complex.

    Evidence Immunoprecipitation of catalytically active RNase P from HeLa cell extracts using polyclonal antibodies raised against recombinant Rpp14

    PMID:10024167

    Open questions at the time
    • Whether RPP14 contacts H1 RNA directly or is peripherally associated through other protein subunits was not determined
    • Stoichiometry of RPP14 within the holoenzyme was not established
  2. 2002 High

    Demonstrating that RPP14 and its partner OIP2 harbor a 3′→5′ phosphorolytic exoribonuclease activity for precursor tRNA 3′-end processing revealed a second catalytic function associated with, but distinct from, RNase P endonuclease activity.

    Evidence In vitro exoribonuclease assays with immunopurified RPP14–OIP2 complex and comparison to purified RNase P, which lacked exonuclease activity

    PMID:11929972

    Open questions at the time
    • The relative contribution of RPP14 versus OIP2 to catalysis was not dissected
    • In vivo relevance of the exoribonuclease activity for tRNA maturation has not been demonstrated
    • Whether RPP14/OIP2 exonuclease activity extends to substrates beyond pre-tRNA is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how RPP14 coordinates its dual roles as an RNase P structural subunit and an exoribonuclease component, what its in vivo substrate scope is, and whether loss of RPP14 selectively disrupts tRNA 3′-end processing versus 5′-leader removal.
  • No in vivo loss-of-function or rescue studies have been reported
  • Structural basis for RPP14 integration into RNase P and interaction with OIP2 is unresolved
  • No disease association has been established through direct genetic evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 1
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
OIP2
Complex memberships
RNase P

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Rpp14 is a protein subunit of human ribonuclease P (RNase P) in HeLa cells; polyclonal antibodies against recombinant Rpp14 recognize its antigen in HeLa cells and precipitate catalytically active RNase P, establishing its association with the enzymatic complex. cDNA cloning, immunoprecipitation of catalytically active RNase P with polyclonal antibodies against recombinant Rpp14 RNA (New York, N.Y.) High 10024167
2002 Rpp14, a subunit of human RNase P, together with its interacting partner OIP2, possesses 3'→5' exoribonuclease activity with a phosphorolytic mechanism that processes the 3' terminus of precursor tRNA; purified RNase P alone lacks this exonuclease activity, indicating Rpp14/OIP2 constitute a distinct exosome-like activity. In vitro exoribonuclease assay, immunoprecipitation of Rpp14 and OIP2, biochemical fractionation of human RNase P complex Proceedings of the National Academy of Sciences of the United States of America High 11929972

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. The EMBO journal 1011 9724636
2000 Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor. Molecular and cellular biology 331 10594030
2002 Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction. Developmental cell 308 12479806
2005 T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia 259 15703784
2001 Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. The American journal of pathology 219 11485924
2001 A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Human molecular genetics 211 11136714
2002 The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nature medicine 201 12091906
2001 Role of p14(ARF) in replicative and induced senescence of human fibroblasts. Molecular and cellular biology 196 11564860
2006 p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis. The Journal of cell biology 172 17178906
2001 Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasia. Proceedings of the National Academy of Sciences of the United States of America 172 11309512
2006 A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14. Nature medicine 146 17195838
2008 Molecular dynamics-solvated interaction energy studies of protein-protein interactions: the MP1-p14 scaffolding complex. Journal of molecular biology 131 18479705
2002 Hypermethylation of the p14(ARF) gene in ulcerative colitis-associated colorectal carcinogenesis. Cancer research 125 11861396
2002 Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia. Cancer research 117 12234999
2010 Expression of Chr9p21 genes CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)) and MTAP in human atherosclerotic plaque. Atherosclerosis 116 20637465
2005 Aureusvirus P14 is an efficient RNA silencing suppressor that binds double-stranded RNAs without size specificity. Journal of virology 110 15890960
2006 Increased frequency of aberrations in the p53/MDM2/p14(ARF) pathway in neuroblastoma cell lines established at relapse. Cancer research 108 16489014
1989 Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. Nature 105 2478889
2002 A major predisposition locus for severe obesity, at 4p15-p14. American journal of human genetics 100 11957135
2000 Adenovirus-mediated p14(ARF) gene transfer in human mesothelioma cells. Journal of the National Cancer Institute 100 10772681
2001 Inactivation of the p14(ARF), p15(INK4B) and p16(INK4A) genes is a frequent event in human oral squamous cell carcinomas. Oral oncology 97 11435176
2002 Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis. Oncogene 92 12082630
2008 TBX3 is overexpressed in breast cancer and represses p14 ARF by interacting with histone deacetylases. Cancer research 90 18245468
2003 Detecting homozygous deletions in the CDKN2A(p16(INK4a))/ARF(p14(ARF)) gene in urinary bladder cancer using real-time quantitative PCR. Clinical cancer research : an official journal of the American Association for Cancer Research 89 12538475
2004 Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes. Proceedings of the National Academy of Sciences of the United States of America 84 15263099
1985 Translocation of c-myc in the hereditary renal cell carcinoma associated with a t(3;8)(p14.2;q24.13) chromosomal translocation. Proceedings of the National Academy of Sciences of the United States of America 84 2995998
2012 Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis. American journal of physiology. Lung cellular and molecular physiology 82 22707614
2000 Alterations and hypermethylation of the p14(ARF) gene in gastric cancer. International journal of cancer 82 10925358
2003 P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Gastroenterology 79 12612901
2002 Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors. Oncogene 78 11965548
2014 The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration. The Journal of cell biology 76 24841562
2000 Immunolocalization of human p14(ARF) to the granular component of the interphase nucleolus. Experimental cell research 76 10772813
2013 Oncomir miR-125b suppresses p14(ARF) to modulate p53-dependent and p53-independent apoptosis in prostate cancer. PloS one 75 23585871
2001 Frequent alterations of the p14(ARF) and p16(INK4a) genes in primary central nervous system lymphomas. Cancer research 72 11522621
2006 Biochemical and NMR analyses of an SF3b155-p14-U2AF-RNA interaction network involved in branch point definition during pre-mRNA splicing. RNA (New York, N.Y.) 69 16495236
2001 E2F-1 up-regulates c-Myc and p14(ARF) and induces apoptosis in colon cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 67 11705881
2012 Transcriptional up-regulation of Sox9 by NF-κB in endometrial carcinoma cells, modulating cell proliferation through alteration in the p14(ARF)/p53/p21(WAF1) pathway. The American journal of pathology 60 22698986
2009 Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine. Urologic oncology 59 19181545
2008 High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 59 18284544
2002 p14(ARF) regulates E2F activity. Oncogene 59 12082609
2002 Human p14(ARF)-mediated cell cycle arrest strictly depends on intact p53 signaling pathways. Oncogene 58 12082636
2009 Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(ARF)-MDM2-p53 axis. Cell death and differentiation 57 19779493
2001 Quantitative real-time PCR does not show selective targeting of p14(ARF) but concomitant inactivation of both p16(INK4A) and p14(ARF) in 105 human primary gliomas. Oncogene 56 11314047
2008 Bmi1 promotes prostate tumorigenesis via inhibiting p16(INK4A) and p14(ARF) expression. Biochimica et biophysica acta 54 18817867
2008 The p14 FAST protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis. Journal of virology 54 18971262
2000 Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. American journal of medical genetics 53 10797439
1999 Rpp14 and Rpp29, two protein subunits of human ribonuclease P. RNA (New York, N.Y.) 48 10024167
2002 p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways. Blood 47 11830494
2013 The late endosomal adaptor molecule p14 (LAMTOR2) represents a novel regulator of Langerhans cell homeostasis. Blood 46 24092934
1995 Assembly of vaccinia virus: incorporation of p14 and p32 into the membrane of the intracellular mature virus. Journal of virology 46 7745704
1988 Translocation t(3;8)(p14.2;q24.1) in renal cell carcinoma affects expression of the common fragile site at 3p14(FRA3B) in lymphocytes. Cancer genetics and cytogenetics 44 3125959
2015 Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer. Epigenetics 43 26291246
2004 Correlation between p14(ARF)/p16(INK4A) expression and HPV infection in uterine cervical cancer. Cancer letters 41 15312681
1999 Functional evidence for a role of combined CDKN2A (p16-p14(ARF))/CDKN2B (p15) gene inactivation in malignant gliomas. Acta neuropathologica 41 10541865
2001 p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease. Clinical cancer research : an official journal of the American Association for Cancer Research 39 11705866
2011 p19(ARF) /p14(ARF) controls oncogenic functions of signal transducer and activator of transcription 3 in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 38 21452288
2007 Hypermethylation of p14 (ARF) may be predictive of colitic cancer in patients with ulcerative colitis. Diseases of the colon and rectum 38 17665255
2007 The clinical importance of Ki-67, p16, p14, and p57 expression in patients with advanced ovarian carcinoma. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 38 17885492
2000 Analysis of JNK, Mdm2 and p14(ARF) contribution to the regulation of mutant p53 stability. Journal of molecular biology 38 10656807
2005 AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene. Oncogene 37 15688012
2006 p53-induced apoptosis occurs in the absence of p14(ARF) in malignant pleural mesothelioma. Neoplasia (New York, N.Y.) 35 16867217
2016 CDKN2A mutations with p14 loss predisposing to multiple nerve sheath tumours, melanoma, dysplastic naevi and internal malignancies: a case series and review of the literature. The British journal of dermatology 34 26876133
2021 CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14ARF degradation. Cell death and differentiation 32 34743205
2006 Differential effect of epigenetic alterations and genomic deletions of CDK inhibitors [p16(INK4a), p15(INK4b), p14(ARF)] in mantle cell lymphoma. Genes, chromosomes & cancer 31 16258956
2006 The p14 fusion-associated small transmembrane (FAST) protein effects membrane fusion from a subset of membrane microdomains. The Journal of biological chemistry 31 16936325
2005 Loss of p21 disrupts p14 ARF-induced G1 cell cycle arrest but augments p14 ARF-induced apoptosis in human carcinoma cells. Oncogene 31 15750619
2017 Ubiquitin specific peptidase 5 mediates Histidine-rich protein Hpn induced cell apoptosis in hepatocellular carcinoma through P14-P53 signaling. Proteomics 29 28523650
2016 Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression. Cancer research 29 27302160
2000 Serine 380 (P14) --> glutamate mutation activates antithrombin as an inhibitor of factor Xa. The Journal of biological chemistry 29 10660568
2019 Aberrant Expression of p14ARF in Human Cancers: A New Biomarker? Tumor & microenvironment 28 30740529
2006 Hypermethylation of hMLH1, HPP1, p14(ARF), p16(INK4A) and APC in primary adenocarcinomas of the small bowel. International journal of cancer 28 16619216
1996 The beta-tubulin monomer release factor (p14) has homology with a region of the DnaJ protein. FEBS letters 28 8955364
2001 CHARGE association with choanal atresia and inner ear hypoplasia in a child with a de novo chromosome translocation t(2;7)(p14;q21.11). American journal of medical genetics 27 11241468
2009 Deregulation of the tumour suppressor genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in basal cell carcinoma. The British journal of dermatology 26 19298278
2004 Alteration of the p14(ARF) gene and p53 status in human hepatocellular carcinomas. Journal of gastroenterology 26 15168247
2002 Recombinant adenovirus-mediated p14(ARF) overexpression sensitizes human breast cancer cells to cisplatin. Biochemical and biophysical research communications 26 12200117
2021 Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the  receptor protein of CRL2Prame complex. Cell death and differentiation 25 33504946
2011 EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1. Cellular oncology (Dordrecht, Netherlands) 25 21538028
2020 Genes and novel sRNAs involved in PAHs degradation in marine bacteria Rhodococcus sp. P14 revealed by the genome and transcriptome analysis. 3 Biotech 24 32206489
2004 Coordinated regulation of replication protein A activities by its subunits p14 and p32. The Journal of biological chemistry 24 15205463
2019 High Positive Correlations between ANRIL and p16-CDKN2A/p15-CDKN2B/p14-ARF Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an ANRIL-ARF Bidirectional Promoter. Non-coding RNA 23 31438464
2015 All-trans retinoic acid induces p53-depenent apoptosis in human hepatocytes by activating p14 expression via promoter hypomethylation. Cancer letters 23 25827071
2014 The late endosomal adaptor molecule p14 (LAMTOR2) regulates TGFβ1-mediated homeostasis of Langerhans cells. The Journal of investigative dermatology 23 25078666
2013 Mutual exclusivity analysis of genetic and epigenetic drivers in melanoma identifies a link between p14 ARF and RARβ signaling. Molecular cancer research : MCR 23 23851445
2013 Biological significance of promoter hypermethylation of p14/ARF gene: relationships to p53 mutational status in Tunisian population with colorectal carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 24065196
2010 EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1. Analytical cellular pathology (Amsterdam) 23 20978327
2001 Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas. Japanese journal of cancer research : Gann 23 11749694
2006 High promoter hypermethylation frequency of p14/ARF in supratentorial PNET but not in medulloblastoma. Histopathology 22 16623784
2015 CDKN2A (p14(ARF)/p16(INK4a)) and ATM promoter methylation in patients with impalpable breast lesions. Human pathology 21 26255234
2013 Promoter hypermethylation of p14 (ARF) , RB, and INK4 gene family in hepatocellular carcinoma with hepatitis B virus infection. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 24254306
2010 Homomultimerization of the reovirus p14 fusion-associated small transmembrane protein during transit through the ER-Golgi complex secretory pathway. The Journal of general virology 21 20861318
2002 Growth suppression by a p14(ARF) exon 1beta adenovirus in human tumor cell lines of varying p53 and Rb status. Cancer gene therapy 21 12224024
1999 Regulated expression of p14 (cofactor A) during spermatogenesis. Cell motility and the cytoskeleton 21 10401580
1991 Chromosomal deletion 4p15.32----p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region. Genomics 21 1684950
2021 Oxaliplatin-Induced Senescence in Colorectal Cancer Cells Depends on p14ARF-Mediated Sustained p53 Activation. Cancers 20 33922007
2015 Human DMTF1β antagonizes DMTF1α regulation of the p14(ARF) tumor suppressor and promotes cellular proliferation. Biochimica et biophysica acta 20 26187004
2012 Significance of MDM2 and P14 ARF polymorphisms in susceptibility to differentiated thyroid carcinoma. Surgery 20 23218882
2011 Loss of p14(ARF) confers resistance to heat shock- and oxidative stress-mediated cell death by upregulating β-catenin. International journal of cancer 20 20549705
2010 Contribution of CDKN2A/P16 ( INK4A ), P14 (ARF), CDK4 and BRCA1/2 germline mutations in individuals with suspected genetic predisposition to uveal melanoma. Familial cancer 20 20842456
2002 A protein subunit of human RNase P, Rpp14, and its interacting partner, OIP2, have 3'-->5' exoribonuclease activity. Proceedings of the National Academy of Sciences of the United States of America 19 11929972