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Scaffold proteins in cancer.

Xu J, Fang JY - Oncoscience (2015)

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China.

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Scaffold proteins are crucial regulators of many key signaling pathways that function by interacting with multiple members of a signaling pathway and tethering them into complexes... However, our recent study reported a RhoGAP-independent function of ArhGAP30, which is implicated in regulating p53 posttranslational modification (PTM)... This substantially increases p53 transcriptional function and promotes cell cycle arrest and apoptosis... Likewise, we also found a non-canonical function of synbindin, which is a subunit of TRAPP (TRAnsport Protein Particle) complex involved in particle transport between organelles... We found that synbindin functions as a scaffold protein that interacts with MEK and ERK on the Golgi apparatus... The interaction promotes phosphorylation of ERK by MEK, and induces cell proliferation and migration... The synbindin LDc domain was found to bind ERK DEF domain, as revealed by our following study... Although the biological roles of ArhGAP30 and synbindin are distinct (anti- and pro-proliferation), their molecular functions are both scaffold proteins that regulate protein PTM... Interestingly, these PTM-related roles do not seem to require their canonical functions, i.e., the RhoGAP enzyme activity of ArhGAP30 and the vesicle trafficking function of synbindin... Also, the functions of these scaffold proteins add to the complexity of PTM processes, as both p53 acetylation and ERK phosphorylation have been reported to be under regulation of various factors... The scaffold protein-mediated PTM may help to explain the prevalence of deregulated p53 and ERK PTM in cancers... As an example, ERK phosphorylation has been found in most gastric cancer tissues, but the alterations in canonical components (such as Ras, Raf and Mek) can only explain some of the abnormal ERK phosphorylation.

No MeSH data available.


Schaffold protein stimulates the modification of protein B by protein AThe examples for both proteins are shown in the lower panel.
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Figure 1: Schaffold protein stimulates the modification of protein B by protein AThe examples for both proteins are shown in the lower panel.


Scaffold proteins in cancer.

Xu J, Fang JY - Oncoscience (2015)

Schaffold protein stimulates the modification of protein B by protein AThe examples for both proteins are shown in the lower panel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549358&req=5

Figure 1: Schaffold protein stimulates the modification of protein B by protein AThe examples for both proteins are shown in the lower panel.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Scaffold proteins are crucial regulators of many key signaling pathways that function by interacting with multiple members of a signaling pathway and tethering them into complexes... However, our recent study reported a RhoGAP-independent function of ArhGAP30, which is implicated in regulating p53 posttranslational modification (PTM)... This substantially increases p53 transcriptional function and promotes cell cycle arrest and apoptosis... Likewise, we also found a non-canonical function of synbindin, which is a subunit of TRAPP (TRAnsport Protein Particle) complex involved in particle transport between organelles... We found that synbindin functions as a scaffold protein that interacts with MEK and ERK on the Golgi apparatus... The interaction promotes phosphorylation of ERK by MEK, and induces cell proliferation and migration... The synbindin LDc domain was found to bind ERK DEF domain, as revealed by our following study... Although the biological roles of ArhGAP30 and synbindin are distinct (anti- and pro-proliferation), their molecular functions are both scaffold proteins that regulate protein PTM... Interestingly, these PTM-related roles do not seem to require their canonical functions, i.e., the RhoGAP enzyme activity of ArhGAP30 and the vesicle trafficking function of synbindin... Also, the functions of these scaffold proteins add to the complexity of PTM processes, as both p53 acetylation and ERK phosphorylation have been reported to be under regulation of various factors... The scaffold protein-mediated PTM may help to explain the prevalence of deregulated p53 and ERK PTM in cancers... As an example, ERK phosphorylation has been found in most gastric cancer tissues, but the alterations in canonical components (such as Ras, Raf and Mek) can only explain some of the abnormal ERK phosphorylation.

No MeSH data available.