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An Sunho,Vo Tam Thuy Lu,Son Taekwon,Choi Hoon,Kim Jinyoung,Lee Juyeon,Kim Byung Hoon,Choe Misun,Ha Eunyoung,Surh Young-Joon,Kim Kyu-Won,Seo Ji Hae 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.
Diverse roles of arrest defective 1 in cancer development
Prerna Chaudhary,Eunyoung Ha,Tam Thuy Lu Vo,Ji Hae Seo 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.12
Arrest defective 1 is an acetyltransferase thatacetylates N-terminal amino acid or internal lysine residuesof its target proteins. By acetylating its target proteins,ARD1 plays roles in many cellular activities, including proliferation,differentiation, autophagy, and apoptosis. In recentyears, a number of investigations have emerged reportingthe dysregulated expression of ARD1 in different types ofcancer, including lung, liver, pancreas, breast, prostate, andcolon cancer. Furthermore, the expression level of ARD1 incancer tissues has been correlated with the progression andmetastasis of the cancer and the survival of cancer patients. Consequently, mechanistic studies have revealed that ARD1-mediated protein acetylation plays an important role in modulatingseveral cellular events that are important for cancerdevelopment, such as cell cycle progression, cell death, andmigration. On the basis of this evidence, targeting of ARD1has been proposed as a promising avenue for the developmentof novel cancer therapeutics. This review summarizesthe biological functions of ARD1 in different types of cancerand provides a deep insight into the biochemical activitiesof ARD1 during tumor progression.
Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis
SEO, JI HAE,PARK, JI-HYEON,LEE, EUN JI,VO, TAM THUY LU,CHOI, HOON,JANG, JAE KYUNG,WEE, HEE-JUN,AHN, BUM JU,CHA, JONG-HO,SHIN, MIN WOOK,KIM, KYU-WON Spandidos Publications 2015 International journal of oncology Vol.46 No.1