[DSRP Evidence](https://dsrpevidence.org/)

# HIFa Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing

## Details

**Authors** Ivan et. al.

**Year** 2001

**Publisher** Science

**Discipline** Biology

[Read it at the publisher](https://doi.org/10.1126/science.1059817) 
10.1126/science.1059817

## In authors' words

### Abstract

HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel–Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe 2+ , this protein modification may play a key role in mammalian oxygen sensing.

### What they set out to do (purpose)

How do cells sense the levels of ambiant oxygen in their environemnts?

### What they found (results)

Cells have an awarness of their environments that is brought upon by stimuli.

## Commentary

### In short

Non-neural entities such as cells have the ability to make distinctions, speaking to the fundamentality of the D,S,R, and P patterns.

### In more detail

Ivan et al 2001 researched how cells are able to sense the levels of ambient oxygen in their environment and react to them, for which they were awarded the 2019 Nobel Prize in Medicine. Specific cellular processes like this one are an example of how Distinctions, Relationships, Perspectives, and Systems may not be merely a pattern of mind, but a pattern of life. Ivan et al. looked at how HIFs

(hypoxia-inducible factors) are a factor that plays an essential role in cellular adaptations to oxygen changes in the environment. HIF binds to DNA to stabilize it in a hypoxic environment, leading to the expression of genes that promote processes like angiogenesis and glucose metabolism. Ivan et al. looked at the relationship between HIF and Von Hippel–Lindau (VHL) disease. VHL is a cancer that is characterized by the development of highly vascular tumors. The protein pVHL in humans is linked to a compound that regulates HIF. It binds with short HIF peptides when the core of the HIF peptide is hydroxylated and destroys it. This core is made up of prolines, which require oxygen and iron to become hydroxylated. Overall, the fact that non-neural entities such as cells are able to make distinctions is not necessarily the most remarkable thing about this discovery. What is remarkable is that every little system in the bodies of all species is based on the ability to perform the D, S, R, and P functions. Thus, the universality of the DSRP functions across all living organisms becomes apparent.

**Patterns it shows** D, S, R, P

**How to cite this** Ivan et. al. (2001). HIFa Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing. Science.