Hypoxia-inducible factor-1 dependent nuclear entry of factor inhibiting HIF-1

October 31, 2015, Society for Experimental Biology and Medicine

The role of FIH-1 in the regulation of HIF-1 transcriptional activity has been known for some time, but is limited to the understanding that in the nucleus FIH-1 hydrolyzes asparagine at the C-terminus of HIF-1α to prevent the interaction between HIF-1α and associated cofactors, resulting in suppressed activation of HIF-1. FIH-1 is a cytoplasmic protein. When does FIH-1 move into the nucleus? This was specifically addressed in Dr. Y. James Kang's laboratory in the Regenerative Medicine Research Center at Sichuan University in China and is reported in the November 2015 issue of Experimental Biology and Medicine.

The researchers used dimethyloxalylglycine (DMOG) to increase the level of intracellular HIF-1α, which was soon found to be localized in the . At the same time the FIH-1 level was also increased in the nucleus. Gene-silencing of HIF-1α dramatically decreased intracellular levels of HIF-1α and eliminated its nuclear location. Under this condition the nuclear entry of FIH-1 was blocked although the total of FIH-1 in the cells was not decreased. Further analysis found that using tetraethylenepentamine (TEPA) to reduce intracellular levels of copper led to a decrease in both intracellular levels of HIF-1α and its nuclear location. Under this condition, the total FIH-1 protein level in the cells was not reduced, but the FIH-1 protein level in the nucleus was dramatically reduced. Therefore, the nuclear entry of FIH-1 is triggered by the process of HIF-1α translocation from the cytoplasm to the nucleus.

Dr. Kang said "Since the increase in the cytoplasmic level of HIF-1α and its nuclear location require the presence of copper, the reduction of intracellular copper levels thus also suppresses the nuclear entry of FIH-1, but does not reduce the total level of FIH-1 in the cells." Further studies are needed to demonstrate how FIH-1 enters into the nucleus and the HIF-1α nuclear entry-dependent regulatory mechanism. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Dr. Kang and colleagues have done an elegant job of demonstrating the role of in FIH-1 nuclear entry."

Explore further: Keeping a lid on inflammation

More information: K. Liang et al. Featured Article: Hypoxia-inducible factor-1 dependent nuclear entry of factor inhibiting HIF-1, Experimental Biology and Medicine (2015). DOI: 10.1177/1535370215570821

Related Stories

Keeping a lid on inflammation

June 17, 2015
Regulatory T cells (Treg cells) are part of the system of checks and balances that prevents the immune response from going overboard and causing autoimmune disease. Although critically important for shaping the immune response ...

Scientists pinpoint bladder cancer patients to benefit from 'tumour-softening'

July 30, 2014
Scientists in Manchester have identified a protein that could help doctors decide which bladder cancer patients would benefit from a treatment that makes radiotherapy more effective, according to a study published in the ...

New study explains why you bulk up with resistance training, not endurance training

October 20, 2015
Resistance and endurance exercises affect the body very differently. These differences suggest that adapting to exercise involves many processes, but scientists have observed that one gene in particular, peroxisome proliferator-activated ...

Hitting inflammation in the guts

November 6, 2013
Researchers in UCD Conway Institute and Systems Biology Ireland have identified a way that a new class of anti-inflammatory drugs may be used to treat inflammatory bowel disease (IBD).

Boosting the body's natural ability to fight urinary tract infections

April 30, 2015
Urinary tract infections (UTIs) are common, and widespread antibiotic resistance has led to urgent calls for new ways to combat them. Researchers at University of California, San Diego School of Medicine and Skaggs School ...

Recommended for you

Clues to obesity's roots found in brain's quality control process

February 20, 2018
Deep in the middle of our heads lies a tiny nub of nerve cells that play a key role in how hungry we feel, how much we eat, and how much weight we gain.

Study looks at how newly discovered gene helps grow blood vessels

February 19, 2018
A new study published today found that a newly discovered gene helps grow blood vessels when it senses inadequate blood flow to tissues.

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.