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The BET family in immunity and disease

Signal Transduction and Targeted Therapy 2021年第2期6卷 387-408页

作者： Nian Wang Runliu Wu Daolin Tang Rui Kang Department of Surgery UT Southwestern Medical CenterDallasTX 75390USA

Innate immunity serves as the rapid and frst-line defense against invading pathogens,and this process can be regulated at various levels,including epigenetic *** bromodomain and extraterminal domain(BET)family of proteins consists of four conserved mammalian members(BRD2,BRD3,BRD4,and BRDT)that regulate the expression of many immunity-associated genes and *** particular,in response to infection and sterile inflammation,abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor(e.g,TLR,NLR,and CGAS)pathways,thereby linking chromatin machinery to innate immunity under disease or pathological ***,the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones(mainly H3 and H4)and recruiting transcription factors(e.g.,RELA)and transcription elongation complex(e.g.P-TEFb)to the chromatin,thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and *** review covers the accumulating data about the roles of the BET family in innate immunity,and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.

关键词： immunity thereby attractive

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Decoding the proteostasis network in resistance to KRAS inhibitors

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The Innovation 2023年第6期4卷 7-8页

作者： Xinxin Song Zhuan Zhou Kenneth D.westover Department of Surgery University of Texas Southwestern Medical CenterDallasTX 75390USA Departments of Radiation Oncology and Biochemistry University of Texas Southwestern Medical CenterDallasTX 75390USA

The Kirsten rat sarcoma(KRAS)gene,which is one of the most frequently mutated genes in human cancers,has long captured the attention of *** recent approval of KRAS G12C inhibitors(KRASi),such as sotorasib and adagrasib,has signaled a promising turn in cancer ***,emerging resistance to these drugs presents a fomidable challenge.'Lv et al's2 publication in Science suggests that the proteostasis network plays a role in mediating diverse KRASi resistance *** work shows that KRAS inhibition suppresses protein quality control in the majority of cancer *** the remaining cells,a subset can reactivate one of the endoplasmic reticulum(ER)stress sensors,specifically the inositol-requiring enzyme 1 alpha(IRE1a)branch of the unfolded protein response(UPR).This adaptation enables the cells to overcome their reliance on oncogenic KRAS,enhancing their resistance to KRASi(Figure 1).This insight underscores the complex interplay be tween oncogenic signaling and protein quality control in scenarios of drug ***,we review and discuss the major findings of this study in the following sections.

关键词： KRAS resistance network

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