Principles of K-Ras effector organization and the role of oncogenic K-Ras in cancer initiation through G1 cell cycle deregulation

Ruth Nussinov*, Chung Jung Tsai, Serena Muratcioglu, Hyunbum Jang, Attila Gursoy, Ozlem Keskin

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Illustrated here is the critical role of oncogenic KRAS in the initiation of cancer through deregulation of the G1 cell cycle, and elements and scenarios taking place under physiological conditions and in KRAS-driven cancer. Raf, PI3K and RalGDS are major K-Ras effectors. They bind at the same Ras site. What decides the cell selection among them? This temporal and spatial decision is critical since in some cellular context the outcome of their signaling pathways may oppose each other. Key among them is the concentration of calcium/calmodulin, negative feedback loops, where a downstream member of the pathway inhibits its upstream activator and cross-inhibition, where inhibition entails blocking another pathway. These three elements, in addition to spatial restrictions by K-Ras-membrane interactions, are not independent; they integrate to provide blueprints for cell decisions. Importantly, elucidation of signaling requires not only K-Ras binary interactions; but the structures and dynamics of its multiprotein complexes.

Original languageEnglish
Pages (from-to)669-682
Number of pages14
JournalExpert Review of Proteomics
Volume12
Issue number6
DOIs
StatePublished - 2 Nov 2015

Funding

FundersFunder number
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010440
Frederick National Laboratory for Cancer Research

    Keywords

    • K-Ras
    • K-Ras4B
    • KRAS4B
    • PI3K
    • Raf
    • RalGDS
    • Ras effectors
    • Ras isoforms
    • calmodulin
    • cell cycle
    • lung cancer
    • pancreatic cancer

    Fingerprint

    Dive into the research topics of 'Principles of K-Ras effector organization and the role of oncogenic K-Ras in cancer initiation through G1 cell cycle deregulation'. Together they form a unique fingerprint.

    Cite this