دورية أكاديمية
أعرض في EDS

Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.

التفاصيل البيبلوغرافية
العنوان: Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.
المؤلفون: Chen LY; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan., Chen LW; Department of Respiratory Care, Chang-Gung University of Science and Technology, Chiayi, Taiwan.; Department of Pediatric Surgery, Chang-Gung Memorial Hospital, Chiayi, Taiwan., Hung CH; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan., Lin CL; Department of Nephrology, Chang-Gung Memorial Hospital, Chiayi, Taiwan., Wang SS; Department of Pediatric Surgery, Chang-Gung Memorial Hospital, Chiayi, Taiwan.; School of Medicine, Chang-Gung University, Taoyuan, Taiwan., Chang PJ; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.; Department of Nephrology, Chang-Gung Memorial Hospital, Chiayi, Taiwan.
المصدر: Microbiology spectrum [Microbiol Spectr] 2022 Feb 23; Vol. 10 (1), pp. e0146421. Date of Electronic Publication: 2022 Jan 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : ASM Press, 2013-
مواضيع طبية MeSH: Caspases/*metabolism , Herpesviridae Infections/*metabolism , Herpesvirus 8, Human/*physiology , Sp3 Transcription Factor/*metabolism, Amino Acid Motifs ; Amino Acid Sequence ; Apoptosis ; Caspases/genetics ; Gene Expression Regulation, Viral ; Herpesviridae Infections/genetics ; Herpesviridae Infections/physiopathology ; Herpesviridae Infections/virology ; Herpesvirus 8, Human/genetics ; Host-Pathogen Interactions ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism ; Lymphoma/genetics ; Lymphoma/metabolism ; Lymphoma/physiopathology ; Lymphoma/virology ; Sequence Alignment ; Sp3 Transcription Factor/chemistry ; Sp3 Transcription Factor/genetics ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Virus Latency
مستخلص: The open reading frame 50 (ORF50) protein of Kaposi's sarcoma-associated herpesvirus (KSHV) is the master regulator essential for initiating the viral lytic cycle. Previously, we have demonstrated that the ORF50 protein can cooperate with Sp3 to synergistically activate a set of viral and cellular gene promoters through highly conserved ORF50-responsive elements that harbor a Sp3-binding motif. Herein, we show that Sp3 undergoes proteolytic cleavage during the viral lytic cycle, and the cleavage of Sp3 is dependent on caspase activation. Since similar cleavage patterns of Sp3 could be detected in both KSHV-positive and KSHV-negative lymphoma cells undergoing apoptosis, the proteolytic cleavage of Sp3 could be a common event during apoptosis. Mutational analysis identifies 12 caspase cleavage sites in Sp3, which are situated at the aspartate (D) positions D17, D19, D180, D273, D275, D293, D304 (or D307), D326, D344, D530, D543, and D565. Importantly, we noticed that three stable Sp3 C-terminal fragments generated through cleavage at D530, D543, or D565 encompass an intact DNA-binding domain. Like the full-length Sp3, the C-terminal fragments of Sp3 could still retain the ability to cooperate with ORF50 protein to activate specific viral and cellular gene promoters synergistically. Collectively, our findings suggest that despite the proteolytic cleavage of Sp3 under apoptotic conditions, the resultant Sp3 fragments may retain biological activities important for the viral lytic cycle or for cellular apoptosis. IMPORTANCE The ORF50 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) is the key viral protein that controls the switch from latency to lytic reactivation. It is a potent transactivator that can activate target gene promoters via interacting with other cellular DNA-binding transcription factors, such as Sp3. In this report, we show that Sp3 is proteolytically cleaved during the viral lytic cycle, and up to 12 caspase cleavage sites are identified in Sp3. Despite the proteolytic cleavage of Sp3, several resulting C-terminal fragments that have intact zinc-finger DNA-binding domains still retain substantial influence in the synergy with ORF50 to activate specific gene promoters. Overall, our studies elucidate the caspase-mediated cleavage of Sp3 and uncover how ORF50 utilizes the cleavage fragments of Sp3 to transactivate specific viral and cellular gene promoters.
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فهرسة مساهمة: Keywords: KSHV; ORF50; Sp3; caspases; proteolytic cleavage; synergistic activation
المشرفين على المادة: 0 (Immediate-Early Proteins)
0 (Rta protein, Human herpesvirus 8)
0 (SP3 protein, human)
0 (Trans-Activators)
148710-94-5 (Sp3 Transcription Factor)
EC 3.4.22.- (Caspases)
تواريخ الأحداث: Date Created: 20220112 Date Completed: 20220307 Latest Revision: 20220307
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8754129
DOI: 10.1128/spectrum.01464-21
PMID: 35019687
قاعدة البيانات: MEDLINE
الوصف
تدمد:2165-0497
DOI:10.1128/spectrum.01464-21