AI Article Synopsis

  • The Ras family G-proteins RalA and RalB play essential but distinct roles in cancer development by helping cells overcome normal limits on growth and survival.
  • RalA is responsible for attaching the exocyst to the cytokinetic furrow during the early stages of cell division, while RalB is needed later at the midbody to facilitate the final separation of daughter cells.
  • Together, RalA and RalB coordinate the exocyst's functions in mitosis by responding to various regulatory signals, highlighting their importance in managing cell division effectively.

Article Abstract

The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2543054PMC
http://dx.doi.org/10.1038/emboj.2008.166DOI Listing

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