Related Experiment Video

Updated: Jun 28, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Kinase requirements in human cells: II. Genetic interaction screens identify kinase requirements following HPV16 E7

Amy Baldwin1, Wenliang Li, Miranda Grace

  • 1The Channing Laboratory, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|October 25, 2008
PubMed

Insights

Human papillomavirus (HPV) oncoproteins hijack cellular pathways. HPV16 E7 oncoprotein alters kinase dependence, identifying novel therapeutic targets like CDK6, ERBB3, FYN, AAK1, and TSSK2 for colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Human papillomavirus (HPV) oncoproteins disrupt cellular signaling pathways, contributing to cancer development.
  • The HPV16 E7 oncoprotein is known to subvert cellular processes, including kinase pathways, during carcinogenesis.

Purpose of the Study:

  • To identify specific kinases targeted by the HPV16 E7 oncoprotein.
  • To understand how HPV16 E7 expression alters cellular dependence on certain kinases for survival.

Main Methods:

  • Utilized shRNA kinase screens in RKO colorectal carcinoma cell lines with and without HPV16 E7 expression.
  • Performed knockdown of identified essential kinases (CDK6, ERBB3, FYN, AAK1, TSSK2) to assess impact on cell viability.

Main Results:

  • Identified CDK6, ERBB3, FYN, AAK1, and TSSK2 as kinases essential for RKO cell survival but not for cells expressing HPV16 E7.
  • Confirmed CDK6 knockdown inhibits pRb phosphorylation, depletes S-phase, and reduces cell viability.
  • Observed similar viability loss upon knockdown of ERBB3, FYN, AAK1, and TSSK2 via an uncharacterized mechanism.

Conclusions:

  • Expression of the HPV16 E7 oncoprotein significantly alters cellular kinase dependency, potentially by degrading pRb.
  • These findings highlight a novel method for unbiased identification of signaling pathways targeted by oncoproteins, analogous to genetic interaction screens.
  • The identified kinases represent potential therapeutic targets in HPV-associated cancers.

More Related Videos

Identification of Kinase-substrate Pairs Using High Throughput Screening11:13

Identification of Kinase-substrate Pairs Using High Throughput Screening

Published on: August 29, 2015

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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...