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The Mystery of Rap1 Suppression of Oncogenic Ras

  1. Author:
    Nussinov,Ruth
    Jang,Hyunbum
    Zhang,Mingzhen
    Tsai,Chung-Jung
    Sablina, Anna A.

  2. Author Address

    NCI, Computat Struct Biol Sect, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, Tel Aviv 69978, Israel.Leuven Canc Inst, VIB Ctr Biol Dis, Leuven, Belgium.Leuven Canc Inst, KU Leuven Dept Oncol, Leuven, Belgium.
    1. Year: 2020
    2. Date: May
    3. Epub Date: 2020 03 02
  2. Journal: Trends in cancer
  3. CELL PRESS,
    1. 6
    2. 5
    3. Pages: 369-379
  5. Type of Article: Review
  6. ISSN: 2405-8025
  1. Abstract:

    Decades ago, Rap1, a small GTPase very similar to Ras, was observed to suppress oncogenic Ras phenotype, reverting its transformation. The proposed reason, persisting since, has been competition between Ras and Rap1 for a common target. Yet, none was found. There was also Rap1's puzzling suppression of Raf-1 versus activation of BRAF. Reemerging interest in Rap1 envisages capturing its Ras suppression action by inhibitors. Here, we review the literature and resolve the enigma. In vivo oncogenic Ras exists in isoform-distinct nanoclusters. The presence of Rap1 within the nanoclusters reduces the number of the clustered oncogenic Ras molecules, thus suppressing Raf-1 activation and mitogen- activated protein kinase (MAPK) signaling. Nanoclustering suggests that Rap1 suppression is Ras isoform dependent. Altogether, a potent Rap1-like inhibitor appears unlikely.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.trecan.2020.02.002
  3. PMID: 32249186
  4. PMCID: PMC7211489
  5. View record in Web of Science®
  6. WOS: 000530165200005

Library Notes

  1. Fiscal Year: FY2019-2020
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