Nav: Home

A possible role for Smurf1 in pulmonary arterial hypertension

June 21, 2010

Pulmonary arterial hypertension (PAH) is a progressive disease, marked by shortness of breath and fatigue which can be fatal if untreated. Increased pressure in the pulmonary artery and its branches is associated with dysfunctional growth control of endothelial and smooth muscle cells leading to excessive thickening of the blood vessel wall, obliteration of the lumen and right heart failure.

BMP (bone morphogenetic protein) receptors play an important role in preventing excess growth of vascular cells. Some individuals with PAH have mutations in BMP receptor (type II). Mutant, and to a lesser extent wild type, receptors are thought to decline in response to disease associated factors such as hypoxia and cytokines. However, the mechanisms leading to the decline in these receptors are not understood.

In the July 2010 issue of Experimental Biology and Medicine, Drs. Murakami, Mathew, Huang, Farahani, Peng, Olson and Etlinger at New York Medical College in Valhalla, NY found that a protein called Smurf1 is elevated in animal models of PAH. This protein is a ubiquitin ligase which can covalently attach ubiquitin to BMP receptors as well as regulate downstream signaling molecules. Such ubiquitin "tagging" leads to receptor endocytosis and degradation by proteasomes and/or lysosomes. Recent studies on cancer cell metastasis have linked Smurf1 with the RhoA/ROCK signaling pathway which has also been implicated in vasoconstriction and vascular remodeling in PAH. Thus, Smurf-1 may have even a broader role in PAH pathogenesis.

The researchers produced PAH in rats by treating with a chemical monocrotaline and in mice by exposure to hypoxia, two well established animal models for the disease. Increased levels of Smurf1 appeared in vascular tissue and could be visualized in endothelial and smooth muscle cells with a time course consistent with a casual role in PAH. Studies with cultured cell lines confirmed Smurf1 dependent degradation of BMP receptors. A mutated Smurf1 which lacked the ability to ligate ubiquitin was able to block BMP receptor degradation acting in a dominant negative manner. Murakami said "these results suggest that Smurf1 may be an attractive therapeutic target to block with agents like dominant negative Smurf-1 mutant or with siRNA constructs etc." Currently treatments for PAH can offer some amelioration of symptoms but no cure is available. Interfering with Smurf1 may offer promise in this regard but future research will need to confirm the role of Smurf1 in human PAH as well as explore the specificity of its actions.

Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Murakami et al have demonstrated an elevation of Smurf 1, a ubiquitin ligase, in rat models of pulmonary arterial hypertension (PAH). Further they have demonstrated that Smurf1 can degrade BMP receptors that have a known relationship to PAH. This suggests that elevation of Smurf1 may play a role in the molecular basis of PAH".
-end-
Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit www.ebmonline.org.

Society for Experimental Biology and Medicine

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
A protein makes the difference
It is well-established knowledge that blood vessels foster the growth of tumors.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
How a protein could become the next big sweetener
High-fructose corn syrup and sugar are on the outs with calorie-wary consumers.
High animal protein intake associated with higher, plant protein with lower mortality rate
The largest study to examine the effects of different sources of dietary protein found that a high intake of proteins from animal sources -- particularly processed and unprocessed red meats -- was associated with a higher mortality rate, while a high intake of protein from plant sources was associated with a lower risk of death.
Protein in, ammonia out
A recent study has compiled and analyzed data from 25 previous studies.

Related Protein Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...