Evidence for allosteric effects on p53 oligomerization induced by phosphorylation
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29124793
PubMed Central
PMC5775181
DOI
10.1002/pro.3344
Knihovny.cz E-zdroje
- Klíčová slova
- CK2, allosteric regulation, conformational change, oligomerization, p53, phosphorylation, protein conformation, protein folding,
- MeSH
- adenosintrifosfát metabolismus MeSH
- alosterická regulace MeSH
- fosforylace MeSH
- kaseinkinasa II metabolismus MeSH
- lidé MeSH
- molekulární modely MeSH
- multimerizace proteinu MeSH
- mutace MeSH
- nádorový supresorový protein p53 chemie genetika metabolismus MeSH
- proteinové domény MeSH
- stabilita proteinů MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- kaseinkinasa II MeSH
- nádorový supresorový protein p53 MeSH
- TP53 protein, human MeSH Prohlížeč
p53 is a tetrameric protein with a thermodynamically unstable deoxyribonucleic acid (DNA)-binding domain flanked by intrinsically disordered regulatory domains that control its activity. The unstable and disordered segments of p53 allow high flexibility as it interacts with binding partners and permits a rapid on/off switch to control its function. The p53 tetramer can exist in multiple conformational states, any of which can be stabilized by a particular modification. Here, we apply the allostery model to p53 to ask whether evidence can be found that the "activating" C-terminal phosphorylation of p53 stabilizes a specific conformation of the protein in the absence of DNA. We take advantage of monoclonal antibodies for p53 that measure indirectly the following conformations: unfolded, folded, and tetrameric. A double antibody capture enzyme linked-immunosorbent assay was used to observe evidence of conformational changes of human p53 upon phosphorylation by casein kinase 2 in vitro. It was demonstrated that oligomerization and stabilization of p53 wild-type conformation results in differential exposure of conformational epitopes PAb1620, PAb240, and DO12 that indicates a reduction in the "unfolded" conformation and increases in the folded conformation coincide with increases in its oligomerization state. These data highlight that the oligomeric conformation of p53 can be stabilized by an activating enzyme and further highlight the utility of the allostery model when applied to understanding the regulation of unstable and intrinsically disordered proteins.
Institute of Biophysics Academy of Sciences of the Czech Republic Brno 612 65 Czech Republic
p53 Laboratory Singapore 138648 Singapore
RECAMO Masaryk Memorial Cancer Institute Brno 65653 Czech Republic
Zobrazit více v PubMed
Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310. PubMed
Fields S, Jang SK (1990) Presence of a potent transcription activating sequence in the p53 protein. Science 249:1046–1049. PubMed
Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C (1993) A proteolytic fragment from the central region of p53 has marked sequence‐specific DNA‐binding activity when generated from wild‐type but not from oncogenic mutant p53 protein. Genes Dev 7:2565–2574. PubMed
Halazonetis TD, Kandil AN (1993) Conformational shifts propagate from the oligomerization domain of p53 to its tetrameric DNA binding domain and restore DNA binding to select p53 mutants. EMBO J 12:5057–5064. PubMed PMC
Wang P, Reed M, Wang Y, Mayr G, Stenger JE, Anderson ME, Schwedes JF, Tegtmeyer P (1994) P53 domains: Structure, oligomerization, and transformation. Mol Cell Biol 14:5182–5191. PubMed PMC
Hupp TR, Meek DW, Midgley CA, Lane DP (1992) Regulation of the specific DNA binding function of p53. Cell 71:875–886. PubMed
Tompa P (2012) On the supertertiary structure of proteins. Nat Chem Biol 8:597–600. PubMed
Neduva V, Linding R, Su‐Angrand I, Stark A, de Masi F, Gibson TJ, Lewis J, Serrano L, Russell RB (2005) Systematic discovery of new recognition peptides mediating protein interaction networks. PLoS Biol 3:e405. PubMed PMC
Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: Re‐assessing the protein structure‐function paradigm. J Mol Biol 293:321–331. PubMed
Hilser VJ (2010) Biochemistry. An ensemble view of allostery. Science 327:653–654. PubMed PMC
Maslon MM, Hrstka R, Vojtesek B, Hupp TR (2010) A divergent substrate‐binding loop within the pro‐oncogenic protein anterior gradient‐2 forms a docking site for reptin. J Mol Biol 404:418–438. PubMed
Uversky VN, Oldfield CJ, Dunker AK (2008) Intrinsically disordered proteins in human diseases: Introducing the d2 concept. Annu Rev Biophys 37:215–246. PubMed
Bullock AN, Henckel J, DeDecker BS, Johnson CM, Nikolova PV, Proctor MR, Lane DP, Fersht AR (1997) Thermodynamic stability of wild‐type and mutant p53 core domain. Proc Natl Acad Sci USA 94:14338–14342. PubMed PMC
Hupp TR, Lane DP (1994) Allosteric activation of latent p53 tetramers. Curr Biol 4:865–875. PubMed
Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E, Xie D (1997) Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36:10117–10124. PubMed
Nichols NM, Matthews KS (2002) Human p53 phosphorylation mimic, s392e, increases nonspecific DNA affinity and thermal stability. Biochemistry 41:170–178. PubMed
Bruins W, Zwart E, Attardi LD, Iwakuma T, Hoogervorst EM, Beems RB, Miranda B, van Oostrom CT, van den Berg J, van den Aardweg GJ, Lozano G, van Steeg H, Jacks T, de Vries A (2004) Increased sensitivity to uv radiation in mice with a p53 point mutation at ser389. Mol Cell Biol 24:8884–8894. PubMed PMC
Hoogervorst EM, Bruins W, Zwart E, van Oostrom CT, van den Aardweg GJ, Beems RB, van den Berg J, Jacks T, van Steeg H, de Vries A (2005) Lack of p53 ser389 phosphorylation predisposes mice to develop 2‐acetylaminofluorene‐induced bladder tumors but not ionizing radiation‐induced lymphomas. Cancer Res 65:3610–3616. PubMed
Yakovleva T, Pramanik A, Kawasaki T, Tan‐No K, Gileva I, Lindegren H, Langel U, Ekstrom TJ, Rigler R, Terenius L, Bakalkin G (2001) p53 latency. C‐terminal domain prevents binding of p53 core to target but not to nonspecific DNA sequences. J Biol Chem 276:15650–15658. PubMed
Ayed A, Mulder FA, Yi GS, Lu Y, Kay LE, Arrowsmith CH (2001) Latent and active p53 are identical in conformation. Nat Struct Biol 8:756–760. PubMed
McKinney K, Mattia M, Gottifredi V, Prives C (2004) P53 linear diffusion along DNA requires its c terminus. Mol Cell 16:413–424. PubMed
Dornan D, Shimizu H, Burch L, Smith AJ, Hupp TR (2003) The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA‐dependent acetylation of p53. Mol Cell Biol 23:8846–8861. PubMed PMC
Češková P, Chichger H, Wallace M, Vojtesek B, Hupp TR (2006) On the mechanism of sequence‐specific DNA‐dependent acetylation of p53: The acetylation motif is exposed upon DNA binding. J Mol Biol 357:442–456. PubMed
Cox ML, Meek DW (2010) Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli. Cell Signal 22:564–571. PubMed
Pospisilova S, Brazda V, Kucharikova K, Luciani MG, Hupp TR, Skladal P, Palecek E, Vojtesek B (2004) Activation of the DNA‐binding ability of latent p53 protein by protein kinase c is abolished by protein kinase ck2. Biochem J 378:939–947. PubMed PMC
Meek DW, Cox M (2011) Induction and activation of the p53 pathway: A role for the protein kinase ck2?. Mol Cell Biochem 356:133–138. PubMed
Bruins W, Bruning O, Jonker MJ, Zwart E, van der Hoeven TV, Pennings JL, Rauwerda H, de Vries A, Breit TM (2008) The absence of ser389 phosphorylation in p53 affects the basal gene expression level of many p53‐dependent genes and alters the biphasic response to uv exposure in mouse embryonic fibroblasts. Mol Cell Biol 28:1974–1987. PubMed PMC
Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H (2001) A DNA damage‐induced p53 serine 392 kinase complex contains ck2, hspt16, and ssrp1. Mol Cell 7:283–292. PubMed
Hupp TR (1999) Regulation of p53 protein function through alterations in protein‐folding pathways. Cell Mol Life Sci 55:88–95. PubMed PMC
Gotz C, Scholtes P, Prowald A, Schuster N, Nastainczyk W, Montenarh M (1999) Protein kinase ck2 interacts with a multi‐protein binding domain of p53. Mol Cell Biochem 191:111–120. PubMed
Jagelska E, Brazda V, Pospisilova S, Vojtesek B, Palecek E (2002) New ELISA technique for analysis of p53 protein/DNA binding properties. J Immunol Methods 267:227–235. PubMed
Appella E, Anderson CW (2000) Signaling to p53: Breaking the posttranslational modification code. Pathol Biol 48:227–245. PubMed
Friedman PN, Chen X, Bargonetti J, Prives C (1993) The p53 protein is an unusually shaped tetramer that binds directly to DNA. Proc Natl Acad Sci USA 90:3319–3323. PubMed PMC
Hamard PJ, Barthelery N, Hogstad B, Mungamuri SK, Tonnessen CA, Carvajal LA, Senturk E, Gillespie V, Aaronson SA, Merad M, Manfredi JJ (2013) The C terminus of p53 regulates gene expression by multiple mechanisms in a target‐ and tissue‐specific manner in vivo. Genes Dev 27:1868–1885. PubMed PMC
Harlow E, Lane D (2006) Antibody purification on protein a or protein g columns. CSH Protoc 2006:pdb.prot4283. PubMed
Vojtĕsek B, Bártek J, Midgley CA, Lane DP (1992) An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151:237–244. PubMed
Dolezalova H, Vojtesek B, Kovarik J (1997) Epitope analysis of the human p53 tumour suppressor protein. Folia Biol 43:49–51. PubMed
Pospisilova S, Kankova K, Svitakova M, Nenutil R, Vojtesek B (2001) New monoclonal antibodies recognizing p53 protein phosphorylated by casein kinase ii at serine 392. Folia Biol 47:148–151. PubMed
Wang PL, Sait F, Winter G (2001) The ‘wildtype’ conformation of p53: Epitope mapping using hybrid proteins. Oncogene 20:2318–2324. PubMed
Milner J, Cook A, Sheldon M (1987) A new anti‐p53 monoclonal antibody, previously reported to be directed against the large t antigen of simian virus 40. Oncogene 1:453–455. PubMed
Vojtesek B, Dolezalova H, Lauerova L, Svitakova M, Havlis P, Kovarik J, Midgley CA, Lane DP (1995) Conformational changes in p53 analysed using new antibodies to the core DNA binding domain of the protein. Oncogene 10:389–393. PubMed
Gannon JV, Greaves R, Iggo R, Lane DP (1990) Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 9:1595–1602. PubMed PMC
Wittig I, Braun HP, Schagger H (2006) Blue native page. Nat Protoc 1:418–428. PubMed
Harlow E, Lane D (2006) Indirect detection using horseradish peroxidase‐labeled reagents. CSH Protoc 2006:pdb.prot4296. PubMed
Characterization of p53 Family Homologs in Evolutionary Remote Branches of Holozoa