Related Experiment Video

Updated: Mar 6, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.4K

p21-activated kinase 4 regulates HIF-1α translation in cancer cells

Hyunju Kim1, Dustin J Woo2, So Yeon Kim3

  • 1Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.

Biochemical and Biophysical Research Communications
|March 15, 2017
PubMed

Insights

Pak4 protein regulates hypoxia-inducible factor-1α (HIF-1α) translation in cervical cancer cells via the Akt-mTOR-4E-BP1 pathway, offering insights into tumor survival under oxygen-deficient conditions.

Area of Science:

  • Cellular signaling pathways
  • Cancer biology
  • Molecular mechanisms of hypoxia

Background:

  • p21-activated kinases (Paks) regulate the actin cytoskeleton and signaling pathways.
  • Pak activation is implicated in human cancer progression.
  • The role of Pak proteins in hypoxic conditions remains largely unexplored.

Purpose of the Study:

  • To investigate the role of Pak proteins in hypoxic cancer cells.
  • To elucidate the specific Pak protein involved in regulating hypoxia-inducible factor-1α (HIF-1α) under hypoxia.
  • To identify the molecular pathway mediating Pak's effect on HIF-1α.

Main Methods:

  • Expression analysis of Pak1 and Pak4 in HeLa cervical cancer cells.
  • Pak4 knockdown experiments under hypoxic conditions.
  • Investigation of the Akt-mTOR-4E-BP1 pathway.

Main Results:

  • Both Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells.
  • Pak4 knockdown, but not Pak1, reduced HIF-1α expression in hypoxia.
  • Pak4 was found to regulate HIF-1α translation through the Akt-mTOR-4E-BP1 pathway under hypoxic conditions.

Conclusions:

  • Pak4 plays a crucial role in regulating HIF-1α in hypoxic cervical cancer cells.
  • A novel connection between Pak4 and HIF-1α in hypoxic tumors is established.
  • Findings provide insights into tumor adaptation and survival mechanisms in oxygen-deficient environments.
Keywords:
4E-BP1AktHIF-1αHypoxiaPak4mTOR

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

878
Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.9K

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...
5.0K
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...
6.0K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
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...
6.1K
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...
8.9K
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...
7.6K