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Gene Review

Pml  -  promyelocytic leukemia

Mus musculus

Synonyms: 1200009E24Rik, AI661194, Protein PML, Trim19
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Disease relevance of Pml


High impact information on Pml

  • In a faithful mouse model of lung cancer, we demonstrate that Pml inactivation leads to increased tumorigenesis [6].
  • We also found that Pml is essential for induction of programmed cell death by Fas, tumour necrosis factor alpha (TNF), ceramide and type I and II interferons (IFNs) [7].
  • The PML-RAR alpha fusion protein of APL renders haemopoietic progenitor cells resistant to Fas-, TNF- and IFN-induced apoptosis with a lack of caspase 3 activation, thus acting as a Pml dominant-negative product [7].
  • These results demonstrate that Pml is a mediator of multiple apoptotic signals, and implicate inhibition of apoptosis in the pathogenesis of APL [7].
  • Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation [8].

Chemical compound and disease context of Pml


Biological context of Pml


Anatomical context of Pml


Associations of Pml with chemical compounds


Physical interactions of Pml


Other interactions of Pml

  • Here, we show that the transcription repressor Daxx and the SWI/SNF protein ATRX are both associated with two intranuclear domains: ND10/PML bodies and heterochromatin [20].
  • Role of SUMO-1-modified PML in nuclear body formation [21].
  • However, these protein aggregates are dissociated in cells producing sufficient IE1 through titration of PML, Daxx, and HDAC-2 [22].
  • We find in a mouse model that Pml loss markedly accelerates tumour onset, incidence and progression in Pten-heterozygous mutants, and leads to female sterility with features that recapitulate the phenotype of Foxo3a knockout mice [23].
  • As a consequence, the progressive reduction in Pml dose leads to inactivation of Foxo3a-mediated transcription of proapoptotic Bim and the cell cycle inhibitor p27(kip1) [23].

Analytical, diagnostic and therapeutic context of Pml


  1. Role of promyelocytic leukemia (PML) protein in tumor suppression. Rego, E.M., Wang, Z.G., Peruzzi, D., He, L.Z., Cordon-Cardo, C., Pandolfi, P.P. J. Exp. Med. (2001) [Pubmed]
  2. Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. He, L.Z., Tribioli, C., Rivi, R., Peruzzi, D., Pelicci, P.G., Soares, V., Cattoretti, G., Pandolfi, P.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Pro-proliferative function of the long isoform of PML-RARalpha involved in acute promyelocytic leukemia. Tussié-Luna, M.I., Rozo, L., Roy, A.L. Oncogene (2006) [Pubmed]
  4. Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice. Zimonjic, D.B., Pollock, J.L., Westervelt, P., Popescu, N.C., Ley, T.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles. Becker, K.A., Florin, L., Sapp, C., Maul, G.G., Sapp, M. J. Virol. (2004) [Pubmed]
  6. A CK2-dependent mechanism for degradation of the PML tumor suppressor. Scaglioni, P.P., Yung, T.M., Cai, L.F., Erdjument-Bromage, H., Kaufman, A.J., Singh, B., Teruya-Feldstein, J., Tempst, P., Pandolfi, P.P. Cell (2006) [Pubmed]
  7. PML is essential for multiple apoptotic pathways. Wang, Z.G., Ruggero, D., Ronchetti, S., Zhong, S., Gaboli, M., Rivi, R., Pandolfi, P.P. Nat. Genet. (1998) [Pubmed]
  8. Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. Lallemand-Breitenbach, V., Zhu, J., Puvion, F., Koken, M., Honoré, N., Doubeikovsky, A., Duprez, E., Pandolfi, P.P., Puvion, E., Freemont, P., de Thé, H. J. Exp. Med. (2001) [Pubmed]
  9. Mouse models of acute promyelocytic leukemia. Pollock, J.L., Westervelt, P., Walter, M.J., Lane, A.A., Ley, T.J. Curr. Opin. Hematol. (2001) [Pubmed]
  10. Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression. Ivanov, V.N., Hei, T.K. Exp. Cell Res. (2006) [Pubmed]
  11. The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage. Salomoni, P., Bernardi, R., Bergmann, S., Changou, A., Tuttle, S., Pandolfi, P.P. Blood (2005) [Pubmed]
  12. Transgenic expression of PML/RARalpha impairs myelopoiesis. Early, E., Moore, M.A., Kakizuka, A., Nason-Burchenal, K., Martin, P., Evans, R.M., Dmitrovsky, E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  13. Cell death induction by the acute promyelocytic leukemia-specific PML/RARalpha fusion protein. Ferrucci, P.F., Grignani, F., Pearson, M., Fagioli, M., Nicoletti, I., Pelicci, P.G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  14. Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation. Muromoto, R., Ishida, M., Sugiyama, K., Sekine, Y., Oritani, K., Shimoda, K., Matsuda, T. J. Immunol. (2006) [Pubmed]
  15. Cloning of the murine homolog of the leukemia-associated PML gene. Goddard, A.D., Yuan, J.Q., Fairbairn, L., Dexter, M., Borrow, J., Kozak, C., Solomon, E. Mamm. Genome (1995) [Pubmed]
  16. Adaptive immunity cooperates with liposomal all-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia. Westervelt, P., Pollock, J.L., Oldfather, K.M., Walter, M.J., Ma, M.K., Williams, A., DiPersio, J.F., Ley, T.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. Isolation and characterization of an acute promyelocytic leukemia cell line selectively resistant to the novel antileukemic and apoptogenic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid. Ponzanelli, I., Giannì, M., Giavazzi, R., Garofalo, A., Nicoletti, I., Reichert, U., Erba, E., Rambaldi, A., Terao, M., Garattini, E. Blood (2000) [Pubmed]
  18. Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein. Nagy, I., Bodmer, M., Schmid, S., Bodmer, D. Hear. Res. (2005) [Pubmed]
  19. Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia. Mitchelmore, C., Kjaerulff, K.M., Pedersen, H.C., Nielsen, J.V., Rasmussen, T.E., Fisker, M.F., Finsen, B., Pedersen, K.M., Jensen, N.A. J. Biol. Chem. (2002) [Pubmed]
  20. Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. Ishov, A.M., Vladimirova, O.V., Maul, G.G. J. Cell. Sci. (2004) [Pubmed]
  21. Role of SUMO-1-modified PML in nuclear body formation. Zhong, S., Müller, S., Ronchetti, S., Freemont, P.S., Dejean, A., Pandolfi, P.P. Blood (2000) [Pubmed]
  22. Mouse cytomegalovirus immediate-early protein 1 binds with host cell repressors to relieve suppressive effects on viral transcription and replication during lytic infection. Tang, Q., Maul, G.G. J. Virol. (2003) [Pubmed]
  23. Identification of a tumour suppressor network opposing nuclear Akt function. Trotman, L.C., Alimonti, A., Scaglioni, P.P., Koutcher, J.A., Cordon-Cardo, C., Pandolfi, P.P. Nature (2006) [Pubmed]
  24. The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1. Lalioti, V.S., Vergarajauregui, S., Pulido, D., Sandoval, I.V. J. Biol. Chem. (2002) [Pubmed]
  25. Mouse models of acute promyelocytic leukemia. Kogan, S.C. Curr. Top. Microbiol. Immunol. (2007) [Pubmed]
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