AI Article Synopsis
- Ras oncoproteins can stimulate cellular growth but may also trigger growth inhibition through processes like senescence, apoptosis, and differentiation, indicating their complex role in cancer biology.
- The effector proteins RASSF1 and Nore1 are implicated in mediating Ras-dependent apoptosis, with Nore1 being frequently down-regulated in lung tumors due to promoter methylation rather than gene deletion.
- Reintroducing Nore1 into lung cancer cells reduces their growth, suggesting it functions as a tumor suppressor alongside RASSF1 within a broader family of Ras effectors.
Article Abstract
Ras oncoproteins mediate multiple biological effects by activating multiple effectors. Classically, Ras activation has been associated with enhanced cellular growth and transformation. However, activated forms of Ras may also inhibit growth by inducing senescence, apoptosis, and differentiation. Induction of apoptosis by Ras may be mediated by its effector RASSF1, which appears to function as a tumor suppressor. We now show that the Ras effector Nore1, which is structurally related to RASSF1, can also mediate a Ras-dependent apoptosis. Moreover, an analysis of Nore1 protein expression showed that it is frequently down-regulated in lung tumor cell lines and primary lung tumors. Like RASSF1, this correlates with methylation of the Nore1 promoter rather than gene deletion. Finally, re-introduction of Nore1, driven by its own promoter, impairs the growth in soft agar of a human lung tumor cell line. Consequently, we propose that the Ras effector Nore1 is a member of a family of Ras effector/tumor suppressors that includes RASSF1.
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| http://dx.doi.org/10.1074/jbc.M211019200 | DOI Listing |
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