scholarly journals Interaction mechanism of endogenous PP2A inhibitor protein ENSA with PP2A

FEBS Journal ◽  
2021 ◽  
Author(s):  
Chandan Thapa ◽  
Pekka Roivas ◽  
Tatu Haataja ◽  
Perttu Permi ◽  
Ulla Pentikäinen
2021 ◽  
Vol 8 ◽  
Author(s):  
Chandan Thapa ◽  
Pekka Roivas ◽  
Tatu Haataja ◽  
Perttu Permi ◽  
Ulla Pentikäinen

Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient secondary structure elements. The interaction mechanism of ARPP-16/19 with PP2A was investigated using microscale thermophoresis and NMR spectroscopy. Our results suggest that ARPP—PP2A A-subunit interaction is mediated by linear motif and has modest affinity whereas, the interaction of ARPPs with B56-subunit is weak and transient. Like many IDPs, ARPPs are promiscuous binders that transiently interact with PP2A A- and B56 subunits using multiple interaction motifs. In summary, our results provide a good starting point for future studies and development of therapeutics that block ARPP-PP2A interactions.


2012 ◽  
Vol &NA; (1432) ◽  
pp. 18
Author(s):  
&NA;

RSC Advances ◽  
2020 ◽  
Vol 10 (35) ◽  
pp. 20862-20871
Author(s):  
Guoyan Ren ◽  
He Sun ◽  
Gen Li ◽  
Jinling Fan ◽  
Lin Du ◽  
...  

The mechanism of interaction between AE and trypsin was studied firstly. The biological activity of both decreased after the interaction. These results provide a basis for the development and utilization of AE.


Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.


2021 ◽  
Vol 289 ◽  
pp. 102360
Author(s):  
Jingyi Wang ◽  
Jiawen Zhang ◽  
Linbo Han ◽  
Jianmei Wang ◽  
Liping Zhu ◽  
...  

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