The researchers began by referencing a previous discovery of their own: certain types of signaling molecules are detected by specific receptors (PDGFRα) in what are known as primary cilia. These cilia are present as single units on nearly all cell types in the human body and they function as cellular antennae that detect and transmit extracellular cues to control embryonic development and maintain tissue and organ function in adults.
The research group has now demonstrated that the very same antennae also play a crucial role in the balancing of the output of PDGFRα signaling so that the signaling doesn't get out of control. Unconstrained, excessive signaling from these receptors increases the risk - of brain tumor and gastrointestinal cancer development.
"Our results demonstrate that, under normal conditions, primary cilia serve to inhibit processes that can lead to cancer. We have shown that specific cancer-inhibiting proteins of the Cbl-family mediate the targeting of PDGFRα to the cilia, and once located in these antennae, the Cbl proteins prevent excessive receptor activation. Further, we have demonstrated that stabilization and functionality of the Cbl proteins are regulated by an entirely new mechanism, which also is associated with the cilia, according to the senior author.
Authors show that intraflagellar transport protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. “Should this mechanism be disturbed, the Cbl proteins will undergo self-destruction, which in turn will lead to mislocalization of the receptors to the general cell surface from where the receptors are wildly over-activated, "says the author.
The result is dramatic because cell antennae will now play an entirely new role in both our understanding of tumor progression and in the development of improved diagnostic and treatment methods for patients affected by certain types of cancer. According to the research group, it is likely that other illnesses are also linked to Cbl-protein protection errors.
"Defects in Cbl proteins are also associated with leukemia and autoimmune diseases. Therefore, our hope is that this discovery will contribute to a better understanding of the mechanisms that lead to these other very complicated illnesses," concludes the author.
http://jcb.rupress.org/content/early/2017/12/12/jcb.201611050
Latest News
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Other Top Stories
A wireless closed-loop system for optogenetic peripheral neuromodul…
Read more
Detecting Alzheimer's disease six months before diagnosis using AI
Read more
Inhalable form of messenger RNA created!
Read more
Safer and more efficient gene editing!
Read more
LEDs to improve health, food!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar