Study on the interaction between the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus and cellular transcription factors = 카포시 육종 허피스 바이러스의 Latency-associated nuclear antigen과 세포 내 전사 조절인자와의 상호작용에 관한 연구

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The latency-associated nuclear antigen (LANA), encoded by the open reading frame (ORF) 73 of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV8), may be required for the persistence of viral episome by tethering it to host chromosome during mitosis. It also has been suggested that LANA may have a transcriptional regulatory activity from its amino acid sequence features. To identify cellular proteins which interact with LANA, yeast two-hybrid assay was performed using full-length LANA as a bait. Among several positive clones was a partial cDNA of activating transcription factor (ATF) 4, also known as cAMP response element (CRE) binding protein (CREB) 2 or tax-response element binding protein (TAXREB) 67. ATF4/CREB2 belongs to the ATF/CREB family of transcription factors, which share the relatively conserved basic region / leucine zipper (bZIP) domain required for DNA binding and homo-/heterodimerization, respectively. In this study, LANA and ATF4/CREB2 were shown to interact in vivo and in vitro, and the putative leucine zipper domain of LANA was required for binding to the bZIP domain of ATF4/CREB2, implicating that the interaction may involve leucine zipper dimerization. Binding of LANA to ATF4/CREB2 resulted in the repression of the transcriptional activation by ATF4/CREB2, but seemed to have no obvious effect on DNA-binding ability of ATF4/CREB2, proved by GAL4 system and electrophoretic mobility shift assay (EMSA). CREB-binding protein (CBP) and its structural/functional homologue, p300, interact with a number of cellular transcription factors, nuclear hormone receptors, coactivators, and viral proteins, thereby participate in cell growth, transformation, and development. The result of preliminary experiment examining the transcriptional role of LANA, and the fact that both p53 and ATF4/CREB2, of which transcriptional activities has been known to be regulated by LANA, utilize CBP as a common coactivator, arose the possibility of the interaction between LAN...
Choe, Joon-Horesearcher최준호researcher
한국과학기술원 : 생물과학과,
Issue Date
165521/325007 / 000993455

학위논문(석사) - 한국과학기술원 : 생물과학과, 2001.2, [ iv, 55 p. ]


ATF4; LANA; KSHV; CREB2; 전사조절인자; 육종; 카포시; CBP

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