KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it is also a known cancer driver gene, with multiple somatic mutations found in a few cancer types. In this study, we looked at eleven missense variants in lung squamous cell carcinoma, one of the most common lung cancer subtypes, to see how they affect the KDM6A catalytic mechanisms. We found that they influence the interaction with histone H3 and the exposure of the trimethylated Lys27, which is critical for wild-type physiological function to varying degrees, by altering the conformational transition.
KDM6A missense variants hamper H3 histone demethylation in lung squamous cell carcinoma / Biagini, Tommaso; Petrizzelli, Francesco; Bianco, SALVATORE DANIELE; Liorni, Niccolo'; Napoli, Alessandro; Castellana, Stefano; Luigi Vescovi, Angelo; Carella, Massimo; Caputo, Viviana; Mazza, Tommaso. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - 20:(2022), pp. 3151-3160. [10.1016/j.csbj.2022.06.041]
KDM6A missense variants hamper H3 histone demethylation in lung squamous cell carcinoma
Tommaso BiaginiCo-primo
;Francesco PetrizzelliCo-primo
;Salvatore Daniele Bianco
;Niccolo' Liorni;Viviana CaputoPenultimo
;
2022
Abstract
KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it is also a known cancer driver gene, with multiple somatic mutations found in a few cancer types. In this study, we looked at eleven missense variants in lung squamous cell carcinoma, one of the most common lung cancer subtypes, to see how they affect the KDM6A catalytic mechanisms. We found that they influence the interaction with histone H3 and the exposure of the trimethylated Lys27, which is critical for wild-type physiological function to varying degrees, by altering the conformational transition.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
