000 03101nam a22004935i 4500
001 978-4-431-54135-6
003 DE-He213
005 20140220083334.0
007 cr nn 008mamaa
008 120720s2012 ja | s |||| 0|eng d
020 _a9784431541356
_9978-4-431-54135-6
024 7 _a10.1007/978-4-431-54135-6
_2doi
050 4 _aQD241-441
072 7 _aPSB
_2bicssc
072 7 _aSCI013040
_2bisacsh
072 7 _aSCI007000
_2bisacsh
082 0 4 _a547
_223
100 1 _aKamada, Rui.
_eauthor.
245 1 0 _aTetramer Stability and Functional Regulation of Tumor Suppressor Protein p53
_h[electronic resource] /
_cby Rui Kamada.
264 1 _aTokyo :
_bSpringer Japan :
_bImprint: Springer,
_c2012.
300 _aXIV, 72 p. 48 illus., 16 illus. in color.
_bonline resource.
336 _atext
_btxt
_2rdacontent
337 _acomputer
_bc
_2rdamedia
338 _aonline resource
_bcr
_2rdacarrier
347 _atext file
_bPDF
_2rda
490 1 _aSpringer Theses, Recognizing Outstanding Ph.D. Research,
_x2190-5053
505 0 _aQuantitative analysis for p53 tetramerization domain mutants reveals a low threshold for tumor suppressor inactivation -- Stabilization of mutant tetrameric structures by calixarene derivatives -- Inhibition of the transcriptional activity of p53 through hetero-oligomerization.
520 _aThis thesis presents the first report of the comprehensive and quantitative analysis of the effects of tumor-derived mutations on the tetrameric structure of tumor suppressor protein p53, which plays a central role in maintaining genomic integrity. Inactivation of p53 via mutation of its gene is a key step in tumorigenesis. Biophysical analyses revealed that the stability of the mutant peptides varied widely. Formation of a tetrameric structure is to be critical for protein–protein interactions, DNA binding, and the post-translational modification of p53. A small destabilization of the tetrameric structure therefore could result in dysfunction of tumor suppressor activity. This work suggests that the threshold for loss of tumor suppressor activity, in terms of the disruption of p53’s tetrameric structure, could be extremely low. Furthermore, functional control of p53 via tetramer formation was demonstrated, based on the structure–function analysis of mutant p53. The results disclosed that relatively small changes in tetramer formation, induced by the stabilization or inhibition of homo-tetramerization, could control p53 function.
650 0 _aChemistry.
650 0 _aBioorganic chemistry.
650 0 _aBiochemistry.
650 0 _aProteomics.
650 1 4 _aChemistry.
650 2 4 _aBioorganic Chemistry.
650 2 4 _aMedicinal Chemistry.
650 2 4 _aProteomics.
710 2 _aSpringerLink (Online service)
773 0 _tSpringer eBooks
776 0 8 _iPrinted edition:
_z9784431541349
830 0 _aSpringer Theses, Recognizing Outstanding Ph.D. Research,
_x2190-5053
856 4 0 _uhttp://dx.doi.org/10.1007/978-4-431-54135-6
912 _aZDB-2-CMS
999 _c104049
_d104049