{"id":80045,"date":"2020-10-01T20:33:30","date_gmt":"2020-10-01T17:33:30","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/researchers-uncover-link-between-phase-separation-and-human-developmental-disorders\/"},"modified":"2020-10-01T20:33:30","modified_gmt":"2020-10-01T17:33:30","slug":"researchers-uncover-link-between-phase-separation-and-human-developmental-disorders","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/researchers-uncover-link-between-phase-separation-and-human-developmental-disorders\/","title":{"rendered":"#Researchers uncover link between phase separation and human developmental disorders"},"content":{"rendered":"

“#Researchers uncover link between phase separation and human developmental disorders<\/strong>”<\/p>\n

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Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NS-ML) are rare human developmental disorders caused by mutations of the protein SHP2. Until recently, the mechanism of NS and NS-ML pathogenesis had been unclear, and nor is there any effective treatment for the disorders.<\/p>\n

Now, however, researchers from the Shanghai Institute of Organic Chemistry (SIOC) of the Chinese Academy of Science<\/a>s have uncovered the mechanism that underlies the pathogenesis of NS and NS-ML.<\/p>\n

They found that disease-associated SHP2 mutants acquire the capacity for liquid-liquid phase separation (LLPS) to boost enzymatic activity, leading to hyperactivation of the downstream cellular signaling pathway.<\/p>\n

Phase separation has emerged as a fundamental mechanism that regulates various biological processes. However, very little is known about whether dysregulation of phase separation plays a role in human developmental disorders.<\/p>\n

The team found that both NS and NS-ML mutations lead to gain-of-function LLPS of SHP2, explaining a long-standing puzzle as to why NS and NS-ML have similar clinical manifestations, although they have different SHP2 mutations.<\/p>\n

According to the researchers, LLPS of SHP2 mutants is regulated by conformational changes in the SHP2 protein, and is potently inhibited by the SHP2 allosteric inhibitor ET070, providing a therapeutic strategy for targeting SHP2 LLPS as a way of treating SHP2-associated developmental disorders.<\/p>\n

This work also suggests the exciting possibility of using LLPS as a pharmaceutical target for developing new drugs.<\/p>\n

The team believes that this study will offer new insights for understanding the link between LLPS and human disease, which will greatly help in the development of therapeutic app<\/a>roaches for treating disease.<\/p>\n\n

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Flow of spinal fluid disrupted in inherited developmental disorder<\/a>\n <\/div>\n

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\n More information:<\/strong>
\n Guangya Zhu et al, Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation, Cell<\/i> (2020). DOI: 10.1016\/j.cell.2020.09.002<\/a><\/p>\n
\n Journal information:<\/strong>
\n Cell<\/cite>
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\n Provided by
\n Chinese Academy of Sciences
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Citation<\/strong>:
\n Researchers uncover link between phase separation and human developmental disorders (2020, October 1)
\n retrieved 1 October 2020
\n from https:\/\/phys.org\/news<\/a>\/2020-10-uncover-link-phase-human-developmental.html<\/p>\n

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\n part may be reproduced without the written permission. The content is provided for information purposes only.<\/p><\/div>\n<\/p><\/div>\n