Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer.

Molecular cancer research : MCR·2026
Same author

Allele-specific antisense oligonucleotide treatment rescues <i>atad3-</i>associated phenotype in zebrafish.

bioRxiv : the preprint server for biology·2026
Same author

ASO-based PKM splice-switching therapy increases anti-CTLA-4 antibody efficacy in pancreatic ductal adenocarcinoma.

Cell discovery·2026
Same author

Exon-Skipping Antisense Oligonucleotides for H3.3K27M-Altered Diffuse Midline Glioma Therapy.

bioRxiv : the preprint server for biology·2026
Same author

Targeting <i>EZH2</i> Oncogenic Splicing: Decoding the Regulatory Network and Antisense Correction.

bioRxiv : the preprint server for biology·2026
Same author

Splice-switching ASOs targeting the AURKA 5' UTR collapse an SRSF1-AURKA-MYC oncogenic circuit in pancreatic cancer.

Molecular cell·2025
Same journal

In This Issue.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Long-term cultural continuity across the Neanderthal-modern human sequence at Üçağızlı II Cave, northern Levant.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Dolphins use names to remember whom to avoid.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Retraction for Shaked and Frenkel, Curiouser and curiouser: Meningeal lymphoid structures in the aging brain.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Small but mighty: The outsized role of small water bodies in the global carbon cycle.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Functional traits produce conditional outcomes in different community contexts.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Related Experiment Video

Updated: Jun 29, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

The splicing-factor oncoprotein SF2/ASF activates mTORC1.

Rotem Karni1, Yoshitaka Hippo, Scott W Lowe

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. rotemka@ekmd.huji.ac.il

Proceedings of the National Academy of Sciences of the United States of America
|October 4, 2008
PubMed
Summary
This summary is machine-generated.

The splicing factor SF2/ASF activates the mTORC1 pathway, driving cancer cell transformation. Inhibiting mTORC1 shows promise for treating SF2/ASF-driven cancers.

More Related Videos

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Related Experiment Videos

Last Updated: Jun 29, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • The splicing factor SF2/ASF is an oncoprotein overexpressed in numerous cancers.
  • The mechanistic target of rapamycin (mTOR) signaling pathway is frequently activated in cancer.
  • mTOR inhibitors are under investigation as anticancer therapeutics.

Purpose of the Study:

  • To investigate the role of the mTOR signaling pathway in SF2/ASF-mediated cellular transformation.
  • To determine which branch of the mTOR pathway is affected by SF2/ASF.
  • To assess the therapeutic potential of targeting mTOR in SF2/ASF-driven cancers.

Main Methods:

  • Assessed mTOR pathway activity via phosphorylation of S6K and eIF4EBP1 in SF2/ASF-transformed cells.
  • Utilized rapamycin to inhibit mTOR activity.
  • Employed shRNA to knock down mTOR, Raptor, and Rictor components.

Main Results:

  • SF2/ASF specifically activates the mTORC1 pathway, evidenced by increased S6K and eIF4EBP1 phosphorylation, without affecting mTORC2 signaling (Akt phosphorylation).
  • mTORC1 activation by SF2/ASF is crucial for cellular transformation, as rapamycin treatment inhibited this process both in vitro and in vivo.
  • Knockdown of mTOR, Raptor, or Rictor using shRNA eliminated the tumorigenic potential of SF2/ASF-overexpressing cells.

Conclusions:

  • SF2/ASF activates mTORC1 independently of upstream PI3K/Akt signaling, and this activation is essential for its oncogenic function.
  • SF2/ASF-driven cancers may exhibit heightened sensitivity to mTOR inhibitors, suggesting a potential targeted therapy approach.