The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network
Open accessAbstract
Nuclear exclusion of the PTEN (phosphatase and tensin homologue deleted in chromosome 10) tumour suppressor has been associated with cancer progression. However, the mechanisms leading to this aberrant PTEN localization in human cancers are currently unknown. We have previously reported that ubiquitinylation of PTEN at specific lysine residues regulates its nuclear-cytoplasmic partitioning. Here we show that functional promyelocytic leukaemia protein (PML) nuclear bodies co-ordinate PTEN localization by opposing the action of a previously unknown PTEN-deubiquitinylating enzyme, herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), and that the integrity of this molecular framework is required for PTEN to be able to enter the nucleus. We find that PTEN is aberrantly localized in acute promyelocytic leukaemia, in which PML function is disrupted by the PML-RARalpha fusion oncoprotein. Remarkably, treatment with drugs that trigger PML-RARalpha degradation, such as all-trans retinoic acid or arsenic trioxide, restore nuclear PTEN. We demonstrate that PML opposes the activity of HAUSP towards PTEN through a mechanism involving the adaptor protein DAXX (death domain-associated protein). In support of this paradigm, we show that HAUSP is overexpressed in human prostate cancer and is associated with PTEN nuclear exclusion. Thus, our results delineate a previously unknown PML-DAXX-HAUSP molecular network controlling PTEN deubiquitinylation and trafficking, which is perturbed by oncogenic cues in human cancer, in turn defining a new deubiquitinylation-dependent model for PTEN subcellular compartmentalization.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The majority of HAUSP is localized in the nucleus”
From USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 (2010) · cites this paper as Song et al., 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform
Rhodes, D. R., Yu, J., Sundaram, S. K., Deshpande, N., Varambally, R., Ghosh, D., Barrette, T. R., Pander, A., & Chinnaiyan, A. M. (2004) · Neoplasia · doi:10.1016/s1476-5586(04)80047-2 · Cited by 3,719
Maehama, T., & Dixon, J. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13375 · Cited by 3,104
Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
Stambolic, V., Suzuki, A., de la Pompa, J. L., Brothers, G. M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J. M., Siderovski, D. P., & Mak, T. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81780-8 · Cited by 2,551
Tenets of PTEN Tumor Suppression
Salmena, L., Carracedo, A., & Pandolfi, P. P. (2008) · Cell · doi:10.1016/j.cell.2008.04.013 · Cited by 1,050
Self-citationEssential role for nuclear PTEN in maintaining chromosomal integrity
Shen, W. H., Balajee, A. S., Wang, J., Wu, H., Eng, C., Pandolfi, P. P., & Yin, Y. (2007) · Cell · doi:10.1016/j.cell.2006.11.042 · Cited by 979
Self-citationStructure, dynamics and functions of promyelocytic leukaemia nuclear bodies
Bernardi, R., & Pandolfi, P. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2277 · Cited by 876
Self-citationRNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
Tatham, M. H., Geoffroy, M., Shen, L., Plechanovová, A., Hattersley, N., Jaffray, E., Palvimo, J. J., & Hay, R. T. (2008) · Nature Cell Biology · doi:10.1038/ncb1716 · Cited by 837
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804
PTEN: One Gene, Many Syndromes
Eng, C. (2003) · Human Mutation · doi:10.1002/humu.10257 · Cited by 787
Ubiquitination regulates PTEN nuclear import and tumor suppression
Trotman, L. C., Wang, X., Alimonti, A., Chen, Z., Teruya-Feldstein, J., Yang, H., Pavletich, N. P., Carver, B. S., Cordon-Cardo, C., Erdjument-Bromage, H., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.040 · Cited by 748
Self-citationArsenic degrades PML or PML–RARα through a SUMO-triggered RNF4/ubiquitin-mediated pathway
Lallemand-Breitenbach, V., Jeanne, M., Benhenda, S., Nasr, R., Lei, M., Pérès, L., Zhou, J., Zhu, J., Raught, B., & de Thé, H. (2008) · Nature Cell Biology · doi:10.1038/ncb1717 · Cited by 726
NEDD4-1 Is a Proto-Oncogenic Ubiquitin Ligase for PTEN
Wang, X., Trotman, L. C., Koppie, T. M., Alimonti, A., Chen, Z., Gao, Z., Wang, J., Erdjument‐Bromage, H., Tempst, P., Cordon‐Cardo, C., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.039 · Cited by 723
Self-citationThe Mechanisms of PML-Nuclear Body Formation
Shen, T. H., Lin, H., Scaglioni, P. P., Yung, T. M., & Pandolfi, P. P. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.09.013 · Cited by 527
Self-citationEverett, R. D., Meredith, M., Orr, A., Cross, A., Kathoria, M., & Parkinson, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.7.1519 · Cited by 491
FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP
van der Horst, A., de Vries-Smits, A. M. M., Brenkman, A. B., van Triest, M. H., van den Broek, N. J. F., Colland, F., Maurice, M. M., & Burgering, B. M. T. (2006) · Nature Cell Biology · doi:10.1038/ncb1469 · Cited by 489
Lallemand-Breitenbach, V., Zhu, J., Puvion-dutilleul, F., Koken, M. H. M., Honoré, N., Doubeikovsky, A., Duprez, E., Pandolfi, P. P., Puvion, E., Freemont, P. S., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.12.1361 · Cited by 488
Self-citationLin, D.-Y., Huang, Y., Jeng, J., Kuo, H.-Y., Chang, C., Chao, T.-T., Ho, C.-C., Chen, Y.-C., Lin, T.-P., Fang, H.-I., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.10.019 · Cited by 434
Disruption of HAUSP gene stabilizes p53.
Cummins, J. M., Rago, C., Kohli, M., Kinzler, K. W., Lengauer, C., & Vogelstein, B. (2004) · Nature · doi:10.1038/nature02501 · Cited by 379
PML regulates p53 stability by sequestering Mdm2 to the nucleolus
Bernardi, R., Scaglioni, P. P., Bergmann, S., Horn, H. F., Vousden, K. H., & Pandolfi, P. P. (2004) · Nature Cell Biology · doi:10.1038/ncb1147 · Cited by 354
Self-citationA CK2-Dependent Mechanism for Degradation of the PML Tumor Suppressor
Scaglioni, P. P., Yung, T. M., Cai, L. F., Erdjument‐Bromage, H., Kaufman, A., Singh, B., Teruya‐Feldstein, J., Tempst, P., & Pandolfi, P. P. (2006) · Cell · doi:10.1016/j.cell.2006.05.041 · Cited by 301
Self-citationMonoubiquitylation promotes mitochondrial p53 translocation
Marchenko, N. D., Wolff, S., Erster, S., Becker, K., & Moll, U. M. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601560 · Cited by 286
Epigenetic PTEN Silencing in Malignant Melanomas without PTEN Mutation
Zhou, X., Gimm, O., Hampel, H., Niemann, T. H., Walker, M. J., & Eng, C. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64627-5 · Cited by 278
Perren, A. A., Komminoth, P., Saremaslani, P., Matter, C., Muletta-Feurer, S., Lees, J. A., Heitz, P. U., & Eng, C. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64624-x · Cited by 265
Critical role for Daxx in regulating Mdm2
Tang, J., Qu, L., Zhang, J., Wang, W., Michaelson, J. S., Degenhardt, Y., El‐Deiry, W. S., & Yang, X. (2006) · Nature Cell Biology · doi:10.1038/ncb1442 · Cited by 242
Whiteman, D. C., Zhou, X., Cummings, M. C., Pavey, S. J., Hayward, N. K., & Eng, C. (2002) · International Journal of Cancer · doi:10.1002/ijc.10294 · Cited by 187
Zhou, X.-P., Loukola, A., Salovaara, R., Nyström, M., Peltomäki, P., de la Chapelle, A., Aaltonen, L. A., & Eng, C. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64200-9 · Cited by 185
Baker, S. J. (2007) · Cell · doi:10.1016/j.cell.2006.12.023 · Cited by 173
Song, M. S., Song, S. J., Kim, S. Y., Oh, H. J., & Lim, D. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.115 · Cited by 137
Self-citationNuclear PTEN-Mediated Growth Suppression Is Independent of Akt Down-Regulation
Liu, J.-L., Sheng, X., Hortobagyi, Z. K., Mao, Z., Gallick, G. E., & Yung, W. K. A. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.6211-6224.2005 · Cited by 108
Tachibana, M., Shibakita, M., Ohno, S., Kinugasa, S., Yoshimura, H., Ueda, S., Fujii, T., Rahman, M. A., Dhar, D. K., & Nagasue, N. (2002) · Cancer · doi:10.1002/cncr.0678 · Cited by 104
Changing venues for tumour suppression: balancing destruction and localization by monoubiquitylation
Salmena, L., & Pandolfi, P. P. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2145 · Cited by 82
Self-citationFridberg, M., Servin, A., Anagnostaki, L., Linderoth, J., Berglund, M., Söderberg, O., Enblad, G., Rosén, A., Mustelin, T., Jerkeman, M., et al. (2007) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190701636443 · Cited by 55
Acute promyelocytic leukemia as a paradigm for targeted therapy
Tallman, M. S. (2004) · Seminars in Hematology · doi:10.1053/j.seminhematol.2004.02.004 · Cited by 47
SnapShot: PTEN Signaling Pathways
Carracedo, A., Salmena, L., & Pandolfi, P. P. (2008) · Cell · doi:10.1016/j.cell.2008.04.023 · Cited by 17
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
Self-citationDeubiquitylating enzymes and drug discovery: emerging opportunities
Harrigan, J. A., Jacq, X., Martin, N. M., & Jackson, S. P. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.152 · Cited by 940
The functions and regulation of the PTEN tumour suppressor: new modes and prospects
Lee, Y.-R., Chen, M., & Pandolfi, P. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0015-0 · Cited by 937
Self-citationBreaking the chains: deubiquitylating enzyme specificity begets function
Clague, M. J., Urbé, S., & Komander, D. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0099-1 · Cited by 878
Metadata
- Authors
- Song, M. S., Salmena, L., Carracedo, A., Egia, A., Lo-Coco, F., Teruya-Feldstein, J., & Pandolfi, P. P.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Pandolfi, Pier Paolo
- Venue
- Nature
- Published
- 2008-08-20
- Volume
- 455
- Issue
- 7214
- Pages
- 813-817
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3398484
- OpenAlex
- W2162648910
- Cited by
- 548
- References
- 34
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 22 · 2023: 35 · 2022: 25 · 2021: 37 · 2020: 43 · 2019: 40 · 2018: 33 · 2017: 39 · 2016: 34 · 2015: 36 · 2014: 32 · 2013: 27 · 2012: 31
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- European Molecular Biology Organization
- National Institutes of Health
- National Cancer Institute (R01CA082328, P50CA092629)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- PTEN, USP7, PML, nuclear localization, PML nuclear bodies, DAXX, PML-RARA fusion, acute promyelocytic leukemia, all-trans retinoic acid, arsenic trioxide, prostate cancer, tumor suppressor regulation, ubiquitination, nuclear-cytoplasmic trafficking
- MeSH terms
- Promyelocytic Leukemia Protein, Ubiquitin-Specific Peptidase 7, Animals, Cell Nucleus, Fibroblasts, Humans, Male, Nuclear Proteins, Prostatic Neoplasms, Transcription Factors, Tretinoin, Ubiquitins, Leukemia, Promyelocytic, Acute, Apoptosis, Molecular Chaperones, Active Transport, Cell Nucleus, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, PTEN Phosphohydrolase, Mice, Ubiquitination, Co-Repressor Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
