Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person In cell culture, p14ARF (CDKN2A transcript 4, CDKN2A-4, ARF)...
| Class:Id | Summation:9646310 |
|---|---|
| _displayName | In cell culture, p14ARF (CDKN2A transcript 4, CDKN2A-4, ARF)... |
| _timestamp | 2023-03-24 16:57:20 |
| created | [InstanceEdit:9646312] Orlic-Milacic, Marija, 2019-05-22 |
| modified | [InstanceEdit:9646314] Orlic-Milacic, Marija, 2019-05-22 [InstanceEdit:9646320] Orlic-Milacic, Marija, 2019-05-22 [InstanceEdit:9646336] Orlic-Milacic, Marija, 2019-05-22 [InstanceEdit:9654136] Orlic-Milacic, Marija, 2019-07-16 [InstanceEdit:9654145] Orlic-Milacic, Marija, 2019-07-16 [InstanceEdit:9654158] Orlic-Milacic, Marija, 2019-07-16 [InstanceEdit:9654168] Orlic-Milacic, Marija, 2019-07-16 [InstanceEdit:9654182] Orlic-Milacic, Marija, 2019-07-16 [InstanceEdit:9658465] Orlic-Milacic, Marija, 2019-08-14 [InstanceEdit:9831738] Orlic-Milacic, Marija, 2023-03-24 |
| text | In cell culture, p14ARF (CDKN2A transcript 4, CDKN2A-4, ARF), one of the two main protein products of the CDKN2A gene, contributes to oncogene induced senescence by stabilizing TP53 (p53). The function of p14ARF in p53 stabilization through sequestration of MDM2, a p53 ubiquitin ligase, depends on the nuclear localization of p14ARF and its ability to interact with MDM2. The nuclear localization signal and the MDM2 interaction domain map to the first 15 amino acids of the N-terminus of p14ARF. This region is encoded by the p14ARF-specific exon 1beta of CDKN2A. An independent MDM2-binding domain localized to the C-terminus of p14ARF (Lohrum et al. 2000). Insertion of 16 nucleotides in exon 1beta results in a frameshift truncation of p14ARF, responsible for a familial melanoma syndrome in which the p16INK4A product of the CDKN2A gene is unaffected. This mutation is rare and has so far been reported in one family only. The mutant protein, p14ARF V22Pfs*46 has the nucleotide localization signal and the N-terminal MDM2 interaction region preserved, but is unable to translocate from the cytosol to the nucleus, possibly due to aberrant conformation (Rizos, Puig et al. 2001), and also lacks the C-terminal MDM2 interaction region. Relocation of wild type p14ARF to the cytosol has been observed in melanoma (Rizos, Darmanian et al. 2001) and aggressive thyroid papillary carcinoma (Ferru et al. 2006). Genomic deletion of exon 1beta, with exons 1alpha, 2 and 3 intact, has been reported in about 30% of melanoma cases with genomic deletions involving the CDKN2A locus (Freedberg et al. 2008). Several different familial melanoma germline mutations map to the exon 1beta splice donor site (Harland et al. 2005). The ability of p14ARF to localize to the nucleolus also plays a role in p14ARF-mediated stabilization of p53. Mutations in exon 2 of the CDKN2A gene can lead to missense mutations in p14ARF that affect its nucleolar localization and p53 stabilization, but the exact mechanism has not been fully elucidated (Zhang and Xiong 1999, reviewed by Fontana et al. 2019). |
| (summation) | [Pathway:9646303] Evasion of Oncogene Induced Senescence Due to p14ARF Defects [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by In cell culture, p14ARF (CDKN2A transcript 4, CDKN2A-4, ARF)... (9646310)
