The neuroprotective marine compound psammaplysene A binds the RNA-binding protein HNRNPK

Marco Boccitto; Nayoung Lee; Satoshi Sakamoto; Lynn A. Spruce; Hiroshi Handa; Jon Clardy; Steven H. Seeholzer; Robert G. Kalb

doi:10.3390/md15080246

The neuroprotective marine compound psammaplysene A binds the RNA-binding protein HNRNPK

Marco Boccitto, Nayoung Lee, Satoshi Sakamoto, Lynn A. Spruce, Hiroshi Handa, Jon Clardy, Steven H. Seeholzer, Robert G. Kalb^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context.

Original language	English (US)
Article number	246
Journal	Marine Drugs
Volume	15
Issue number	8
DOIs	https://doi.org/10.3390/md15080246
State	Published - Aug 2017

Funding

Acknowledgments: This work was supported by the US Public Health Service (NS 052325).

Keywords

Foxo
HNRNPK
Neurodegeneration
Psammaplysene A
RNA metabolism

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/md15080246

Cite this

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title = "The neuroprotective marine compound psammaplysene A binds the RNA-binding protein HNRNPK",

abstract = "In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context.",

keywords = "Foxo, HNRNPK, Neurodegeneration, Psammaplysene A, RNA metabolism",

author = "Marco Boccitto and Nayoung Lee and Satoshi Sakamoto and Spruce, {Lynn A.} and Hiroshi Handa and Jon Clardy and Seeholzer, {Steven H.} and Kalb, {Robert G.}",

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year = "2017",

month = aug,

doi = "10.3390/md15080246",

language = "English (US)",

volume = "15",

journal = "Marine Drugs",

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T1 - The neuroprotective marine compound psammaplysene A binds the RNA-binding protein HNRNPK

AU - Boccitto, Marco

AU - Lee, Nayoung

AU - Sakamoto, Satoshi

AU - Spruce, Lynn A.

AU - Handa, Hiroshi

AU - Clardy, Jon

AU - Seeholzer, Steven H.

AU - Kalb, Robert G.

PY - 2017/8

Y1 - 2017/8

N2 - In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context.

AB - In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context.

KW - Foxo

KW - HNRNPK

KW - Neurodegeneration

KW - Psammaplysene A

KW - RNA metabolism

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The neuroprotective marine compound psammaplysene A binds the RNA-binding protein HNRNPK

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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