MDM2 and mitochondrial function: One complex intersection

被引:13
|
作者
Rubio-Patino, Camila [1 ,2 ]
Trotta, Andrew Paul [1 ,2 ]
Chipuk, Jerry Edward [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Oncol Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Tisch Canc Inst, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Dept Dermatol, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[5] Icahn Sch Med Mt Sinai, Dept Dermatol, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[6] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
关键词
Apoptosis; Bioenergetics; Complex I; Electron transport chain; MDM2; Mitochondria; Oncogene; p53; Tumor suppressor; DEPENDENT PROTEIN-KINASE; DNA-ENCODED SUBUNITS; P53; PROTEIN; OXIDATIVE-PHOSPHORYLATION; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; ELECTRON-TRANSPORT; GENE AMPLIFICATION; OVEREXPRESSION; CANCER;
D O I
10.1016/j.bcp.2018.10.032
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Decades of research reveal that MDM2 participates in cellular processes ranging from macro-molecular metabolism to cancer signaling mechanisms. Two recent studies uncovered a new role for MDM2 in mitochondrial bioenergetics. Through the negative regulation of NDUFS1 (NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1) and MT-ND6 (NADH dehydrogenase 6), MDM2 decreases the function and efficiency of Complex I (CI). These observations propose several important questions: (1) Where does MDM2 affect CI activity? (2) What are the cellular consequences of MDM2-mediated regulation of CI? (3) What are the physiological implications of these interactions? Here, we will address these questions and position these observations within the MDM2 literature.
引用
收藏
页码:14 / 20
页数:7
相关论文
共 50 条
  • [31] MDM2 variant in tumorigenesis
    Vogan, K
    NATURE GENETICS, 2005, 37 (01) : 17 - 17
  • [32] Mdm2: The Ups and Downs
    Tamar Juven-Gershon
    Moshe Oren
    Molecular Medicine, 1999, 5 : 71 - 83
  • [33] Posttransiational modification of MDM2
    Meek, DW
    Knippschild, U
    MOLECULAR CANCER RESEARCH, 2003, 1 (14) : 1017 - 1026
  • [34] Conditional inactivation of Mdm2
    Mary Ellen Perry
    Susan Mendrysa
    Nature Genetics, 2001, 27 (Suppl 4) : 78 - 79
  • [35] MDM2 in breast cancer
    Masakazu Toi
    Shigehira Saji
    Akio Suzuki
    Yutaka Yamamoto
    Takeshi Tominaga
    Breast Cancer, 1997, 4 (4) : 264 - 268
  • [36] Mdm2 as a chromatin modifier
    Wienken, Magdalena
    Moll, Ute M.
    Dobbelstein, Matthias
    JOURNAL OF MOLECULAR CELL BIOLOGY, 2017, 9 (01) : 74 - 80
  • [37] The molecular dynamics of MDM2
    Nicholson, Judith
    Hupp, Ted R.
    CELL CYCLE, 2010, 9 (10) : 1878 - 1881
  • [38] Functions of the MDM2 oncoprotein
    D. A. Freedman
    L. Wu
    A. J. Levine
    Cellular and Molecular Life Sciences CMLS, 1999, 55 : 96 - 107
  • [39] Mdm2: Open questions
    Dobbelstein, Matthias
    Levine, Arnold J.
    CANCER SCIENCE, 2020, 111 (07) : 2203 - 2211
  • [40] Functions of the MDM2 oncoprotein
    Freedman, DA
    Wu, L
    Levine, AJ
    CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (01) : 96 - 107