Related Experiment Video
Updated: May 15, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1
Vered Ben-Hur1, Polina Denichenko, Zahava Siegfried
1Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Abstract:
Ribosomal S6 kinase 1 (S6K1) is a major mTOR downstream signaling molecule that regulates cell size and translation efficiency. Here, we report that short isoforms of S6K1 are overproduced in breast cancer cell lines and tumors. Overexpression of S6K1 short isoforms induces transformation of human breast epithelial cells. The long S6K1 variant (Iso-1) induced opposite effects. It inhibits Ras-induced transformation and tumor formation, while its knockdown or knockout induces transformation, suggesting that Iso-1 has a tumor-suppressor activity. Furthermore, we found that S6K1 short isoforms bind and activate mTORC1, elevating 4E-BP1 phosphorylation, cap-dependent translation, and Mcl-1 protein levels. Both a phosphorylation-defective 4E-BP1 mutant and the mTORC1 inhibitor rapamycin partially blocked the oncogenic effects of S6K1 short isoforms, suggesting that these are mediated by mTORC1 and 4E-BP1. Thus, alternative splicing of S6K1 acts as a molecular switch in breast cancer cells, elevating oncogenic isoforms that activate mTORC1.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
RNA Splicing
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

