HAT Histone Acetyl Transferase s Attività anomale da parte degli enzimi HDACs sono state evidenziate in molti diversi tipi di cancro, come la leucemia promielocitica, la leucemia mielogena acuta, il linfoma di non-Hodgkin, e altri tipi di carcinomi colorettali e gastrici. Quando questi enzimi agiscono in modo "scorretto," possono 3 HAT Families
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HAT Histone Acetyl Transferases Attività anomale da parte degli enzimi HDACs sono state evidenziate in molti diversi tipi di cancro, come la leucemia promielocitica,
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HATHistone Acetyl Transferases
Attività anomale da parte degli enzimi HDACs sono state evidenziate in molti diversi tipi di cancro, come la leucemia promielocitica, la leucemia mielogena acuta, il linfoma di non-Hodgkin, e altri tipi di carcinomi colorettali e gastrici. Quando questi enzimi agiscono in modo "scorretto," possono impedire la trascrizione di geni fondamentali.
3 HAT Families
KAT3 Family: p300 (E1Abinding protein) and CBP(CREB binding protein)
Rubinstein–Taybi syndrome (RTS) is a developmental disorder caused by heterozygous germline mutations (point mutations, translocations or deletions) of the CBP gene. RTS is characterized by broad thumbs, cranio-facial and cardiac abnormalities, as well as mental retardation. Patients with RTS have an increased predisposition to cancer
P300/CBP in cancer
M4/M5 subtype of acute myeloid leukemia (AML) This translocation fuses the gene encoding the monocytic leukemia zinc- finger protein (MOZ) with the amino terminus of CBP. aberrant acetylation
MLL-CBP and MLL-p300 translocations (MLL-mixed lineage leukemia) have alsobeen described.(AML) aberrant acetylation and methylation
Mutations in CBP or P300 are correlated with different type of tumors
Chromosomal rearrangements involve CBP more commonly than p300.
HDAC-Histone Deacetylase
Classe1: omologo yRPD3 (dominio HDAC,nucleari)Classe2: omologo yHDA1(dominio HDAC, nucleari/citoplasmatiche(P))Classe 3: ySIRT2Classe 4:classificato per omologia di sequenza
HDAC-Histone Deacetylase
Classe 2a: residui forforilati conservati molto importanti per il shuttling tra nucleo e cytClasse 2b : ha due domini HDAC consecutivi
HDAC classe3 : Sir
Sirtuin-mediated deacetylation reaction couples lysine deacetylation to NAD hydrolysisSir2 family deacetylation target consensus sequences. The amino acid sequence of the Sir2 targets are shown: histone H3 lysine 9; histone H3 lysine 14; histone H4 lysine 16; p53 lysine 382; Tubulin, alba.