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PHF1  -  PHD finger protein 1

Homo sapiens

Synonyms: MTF2L2, PCL1, PHF2, Polycomb-like protein 1, Protein PHF1, ...
 
 
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Disease relevance of PHF1

 

High impact information on PHF1

  • The PHD finger may promote both gene expression and repression through interactions with trimethylated lysine 4 on histone 3 (H3K4), a universal modification at the beginning of active genes [5].
  • Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage [6].
  • We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs [7].
  • We demonstrate that the tandem PHD finger and bromodomain of KAP-1, an arrangement often found in cofactor proteins but functionally ill-defined, form a cooperative unit that is required for transcriptional repression [8].
  • Moreover, single amino acid substitutions in either the bromodomain or PHD finger, including ones that mimic disease-causing mutations in the hATRX PHD finger, abolish repression [8].
 

Chemical compound and disease context of PHF1

 

Biological context of PHF1

  • The PHF1 gene encodes a protein with two zinc finger motifs whose involvement in tumorigenesis and/or tumor progression has not been reported before, but its rearrangement clearly defines a new pathogenetic subgroup of ESS [11].
  • The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia [11].
  • Tau phosphorylation by proline-directed and non-proline-directed protein kinases has been tested using antibodies PHF1 and 12E8, respectively [10].
  • We report here that continuous exposure to 5 microM non-fibrillar Abeta40 or Abeta42 kills primary brain cells by apoptosis within 2-3 weeks, Abeta42 is more toxic and selective for neurons than Abeta40, and Abeta42, but not Abeta40, induces a transient increase in neurons that are positive for the AD-like PHF1 epitope [12].
  • Yng1 PHD Finger Binding to H3 Trimethylated at K4 Promotes NuA3 HAT Activity at K14 of H3 and Transcription at a Subset of Targeted ORFs [13].
 

Anatomical context of PHF1

  • Degenerating neurons from the AD hippocampus, compared to neurons from the normal aged hippocampus, exhibited increased immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase [14].
  • The modulation of tau phosphorylation at Serl99/Ser202, Ser396/Ser404, Ser262/Ser356, and Thr181 sites was examined in these cell lines using the phosphorylation state-dependent antitau antibodies Tau 1, PHF1, 12E8, and AT270 [15].
  • Specifically, we investigated the correspondence of immunoreactivity for Jun and Fos proteins with immunoreactivity for paired helical filament-1 (PHF-1), a marker for neurofibrillary tangles which recognizes abnormally phosphorylated tau, glial fibrillary acidic protein (GFAP), and thioflavine staining in double-labeling experiments [16].
  • In general, these IL-8RB-positive neurities do not co-localize with PHF-1 or AT8 (hyperphosphorylated tau) immunoreactive neurites but instead co-localize with beta PP-positive neurites [17].
  • AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs [18].
 

Associations of PHF1 with chemical compounds

  • The structure unequivocally exhibits the canonical PHD finger fold, with a highly conserved tryptophan buried inside the structure [19].
  • Like TIF1 alpha, TIF1 beta also contains an additional Cys/His cluster (PHD finger) and a bromo-related domain [20].
  • Free-floating (40 microm) and paraffin-embedded (12 microm) sections of formalin fixed frontal cortex from mild, moderate, and severe AD cases (n = 18) were pretreated with fifteen different protocols and stained with each of the following antibodies: beta42, PHF-1, MC-1 and AT8 [21].
  • Laminin also caused an increase of PHF-1 tau in retinoic acid-treated cells [9].
  • Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404 [22].
 

Enzymatic interactions of PHF1

  • Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Delta9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment [23].
  • c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis [24].
 

Other interactions of PHF1

  • An association was also observed between PHF1 and EZH2, human homologs of PCL and E(Z), respectively, demonstrating the evolutionary conservation of this interaction [25].
  • Several phosphorylation-dependent antibodies (i.e. AT270, AT8, AT180, T3P, and PHF1) that recognize PHF-tau also recognized these tau isoforms, albeit at reduced levels in the mature rat brain [26].
  • Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor [27].
  • MLL5 includes a SET domain and a single PHD finger, but lacks A-T hooks and methyltransferase homology domains that are found in MLL [28].
  • We have isolated and characterized a novel PHD finger gene, PHF2, which maps to human Chromosome (Chr) 9q22 close to D9S196 [29].
 

Analytical, diagnostic and therapeutic context of PHF1

References

  1. Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome. Kalkhoven, E., Roelfsema, J.H., Teunissen, H., den Boer, A., Ariyurek, Y., Zantema, A., Breuning, M.H., Hennekam, R.C., Peters, D.J. Hum. Mol. Genet. (2003) [Pubmed]
  2. The yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone h3. Martin, D.G., Baetz, K., Shi, X., Walter, K.L., Macdonald, V.E., Wlodarski, M.J., Gozani, O., Hieter, P., Howe, L. Mol. Cell. Biol. (2006) [Pubmed]
  3. Reversible heat stress-related loss of phosphorylated Alzheimer-type epitopes in Tau proteins of human neuroblastoma cells. Chiang, M.F., Liu, W.K., Yen, S.H. J. Neurosci. (1993) [Pubmed]
  4. Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. Shamay, M., Barak, O., Doitsh, G., Ben-Dor, I., Shaul, Y. J. Biol. Chem. (2002) [Pubmed]
  5. It takes a PHD to read the histone code. Mellor, J. Cell (2006) [Pubmed]
  6. The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Gozani, O., Karuman, P., Jones, D.R., Ivanov, D., Cha, J., Lugovskoy, A.A., Baird, C.L., Zhu, H., Field, S.J., Lessnick, S.L., Villasenor, J., Mehrotra, B., Chen, J., Rao, V.R., Brugge, J.S., Ferguson, C.G., Payrastre, B., Myszka, D.G., Cantley, L.C., Wagner, G., Divecha, N., Prestwich, G.D., Yuan, J. Cell (2003) [Pubmed]
  7. Positional cloning of the APECED gene. Nagamine, K., Peterson, P., Scott, H.S., Kudoh, J., Minoshima, S., Heino, M., Krohn, K.J., Lalioti, M.D., Mullis, P.E., Antonarakis, S.E., Kawasaki, K., Asakawa, S., Ito, F., Shimizu, N. Nat. Genet. (1997) [Pubmed]
  8. Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Schultz, D.C., Friedman, J.R., Rauscher, F.J. Genes Dev. (2001) [Pubmed]
  9. Alzheimer's-associated phospho-tau epitope in human neuroblastoma cell cultures: up-regulation by fibronectin and laminin. Martin, H., Lambert, M.P., Barber, K., Hinton, S., Klein, W.L. Neuroscience (1995) [Pubmed]
  10. Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells. Gómez-Ramos, A., Díaz-Nido, J., Smith, M.A., Perry, G., Avila, J. J. Neurosci. Res. (2003) [Pubmed]
  11. Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Micci, F., Panagopoulos, I., Bjerkehagen, B., Heim, S. Cancer Res. (2006) [Pubmed]
  12. Cultured cell and transgenic mouse models for tau pathology linked to beta-amyloid. Bloom, G.S., Ren, K., Glabe, C.G. Biochim. Biophys. Acta (2005) [Pubmed]
  13. Yng1 PHD Finger Binding to H3 Trimethylated at K4 Promotes NuA3 HAT Activity at K14 of H3 and Transcription at a Subset of Targeted ORFs. Taverna, S.D., Ilin, S., Rogers, R.S., Tanny, J.C., Lavender, H., Li, H., Baker, L., Boyle, J., Blair, L.P., Chait, B.T., Patel, D.J., Aitchison, J.D., Tackett, A.J., Allis, C.D. Mol. Cell (2006) [Pubmed]
  14. Localization of transglutaminase in hippocampal neurons: implications for Alzheimer's disease. Appelt, D.M., Kopen, G.C., Boyne, L.J., Balin, B.J. J. Histochem. Cytochem. (1996) [Pubmed]
  15. Dephosphorylation of tau protein by calcineurin triturated into neural living cells. Wei, Q., Holzer, M., Brueckner, M.K., Liu, Y., Arendt, T. Cell. Mol. Neurobiol. (2002) [Pubmed]
  16. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer's disease: association with pathology. Anderson, A.J., Cummings, B.J., Cotman, C.W. Exp. Neurol. (1994) [Pubmed]
  17. Interleukin-8 receptor B immunoreactivity in brain and neuritic plaques of Alzheimer's disease. Xia, M., Qin, S., McNamara, M., Mackay, C., Hyman, B.T. Am. J. Pathol. (1997) [Pubmed]
  18. Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins. Scott, H.S., Heino, M., Peterson, P., Mittaz, L., Lalioti, M.D., Betterle, C., Cohen, A., Seri, M., Lerone, M., Romeo, G., Collin, P., Salo, M., Metcalfe, R., Weetman, A., Papasavvas, M.P., Rossier, C., Nagamine, K., Kudoh, J., Shimizu, N., Krohn, K.J., Antonarakis, S.E. Mol. Endocrinol. (1998) [Pubmed]
  19. NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease. Bottomley, M.J., Stier, G., Pennacchini, D., Legube, G., Simon, B., Akhtar, A., Sattler, M., Musco, G. J. Biol. Chem. (2005) [Pubmed]
  20. Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Moosmann, P., Georgiev, O., Le Douarin, B., Bourquin, J.P., Schaffner, W. Nucleic Acids Res. (1996) [Pubmed]
  21. Optimization of techniques for the maximal detection and quantification of Alzheimer's-related neuropathology with digital imaging. Cummings, B.J., Mason, A.J., Kim, R.C., Sheu, P.C., Anderson, A.J. Neurobiol. Aging (2002) [Pubmed]
  22. Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404. Otvos, L., Feiner, L., Lang, E., Szendrei, G.I., Goedert, M., Lee, V.M. J. Neurosci. Res. (1994) [Pubmed]
  23. Endogenous overproduction of beta-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells. Wang, Y.P., Wang, X.C., Tian, Q., Yang, Y., Zhang, Q., Zhang, J.Y., Zhang, Y.C., Wang, Z.F., Wang, Q., Li, H., Wang, J.Z. Journal of neural transmission (Vienna, Austria : 1996) (2006) [Pubmed]
  24. c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis. Tatebayashi, Y., Planel, E., Chui, D.H., Sato, S., Miyasaka, T., Sahara, N., Murayama, M., Kikuchi, N., Yoshioka, K., Rivka, R., Takashima, A. FASEB J. (2006) [Pubmed]
  25. Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein. O'Connell, S., Wang, L., Robert, S., Jones, C.A., Saint, R., Jones, R.S. J. Biol. Chem. (2001) [Pubmed]
  26. The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases. Mawal-Dewan, M., Henley, J., Van de Voorde, A., Trojanowski, J.Q., Lee, V.M. J. Biol. Chem. (1994) [Pubmed]
  27. PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme. Struss, A.K., Romeike, B.F., Munnia, A., Nastainczyk, W., Steudel, W.I., König, J., Ohgaki, H., Feiden, W., Fischer, U., Meese, E. Oncogene (2001) [Pubmed]
  28. MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Emerling, B.M., Bonifas, J., Kratz, C.P., Donovan, S., Taylor, B.R., Green, E.D., Le Beau, M.M., Shannon, K.M. Oncogene (2002) [Pubmed]
  29. PHF2, a novel PHD finger gene located on human chromosome 9q22. Hasenpusch-Theil, K., Chadwick, B.P., Theil, T., Heath, S.K., Wilkinson, D.G., Frischauf, A.M. Mamm. Genome (1999) [Pubmed]
  30. The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster. Coulson, M., Robert, S., Eyre, H.J., Saint, R. Genomics (1998) [Pubmed]
  31. Comparison of the neurofibrillary pathology in Alzheimer's disease and familial presenile dementia with tangles. Spillantini, M.G., Crowther, R.A., Goedert, M. Acta Neuropathol. (1996) [Pubmed]
  32. Cell cycle-dependent phosphorylation and microtubule binding of tau protein stably transfected into Chinese hamster ovary cells. Preuss, U., Döring, F., Illenberger, S., Mandelkow, E.M. Mol. Biol. Cell (1995) [Pubmed]
  33. High prevalence of thorn-shaped astrocytes in the aged human medial temporal lobe. Schultz, C., Ghebremedhin, E., Del Tredici, K., Rüb, U., Braak, H. Neurobiol. Aging (2004) [Pubmed]
 
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