Sung-Kyun Park, Xiaorong Zhou, Kathryn E. Pendleton, Olga V. Hunter, Jennifer J. Kohler, Kathryn A. O’Donnell, Nicholas K. Conrad
언어
영어(ENG)
URL
https://www.earticle.net/Article/A346256
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원문정보
초록
영어
Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS) that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein. However, the ISS-deleted cells are hypersensitive to OGA inhibition in culture and in soft agar. Moreover, growth of xenograft tumors from ISS-deleted cells is compromised in mice treated with an OGA inhibitor. Thus, ISS-mediated regulation of OGT intron retention is a key component in OGT expression and maintaining O-GlcNAc homeostasis.
저자
Sung-Kyun Park [ Infectious Diseases Research Center, Division of Biomedical Sciences, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea, Department of Microbiology University of Texas Southwestern Medical Center, Dallas, USA ]
Xiaorong Zhou [ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, USA ]
Kathryn E. Pendleton [ Department of Microbiology University of Texas Southwestern Medical Center, Dallas, USA ]
Olga V. Hunter [ Department of Microbiology University of Texas Southwestern Medical Center, Dallas, USA ]
Jennifer J. Kohler [ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, USA ]
Kathryn A. O’Donnell [ Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA ]
Nicholas K. Conrad [ Department of Microbiology University of Texas Southwestern Medical Center, Dallas, USA ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.