The Therapeutic Potential of PTEN Modulation: Targeting Strategies from Gene to Protein

Research output: Contribution to JournalReview articleAcademicpeer-review

Abstract

Two decades have passed since the discovery of the tumor suppressor, PTEN. A multitude of biological functions have since been revealed, suggesting potential therapeutic applications for both PTEN activation (e.g., cancer) and inhibition (e.g., neuroregeneration). Nevertheless, PTEN's therapeutic suitability has been called into question due to its “risky” profile as a tumor suppressor. To evaluate PTEN function and its various roles in disease a number of molecules have so far been developed. However, intrinsic problems associated with phosphatase inhibition and PTEN's complex regulation via post-translational modifications hinder straightforward access to selective modulators. For this reason, central questions associated with PTEN targeting remain unanswered. In this perspective, we summarize current PTEN-targeting strategies and discuss potential approaches to modulate its functional dose, considering all stages of PTEN biogenesis from direct protein modulation to the targeting of relevant miRNAs as well as the PTEN gene and mRNA
Original languageEnglish
Pages (from-to)19-29
JournalCell Chemical Biology
Volume25
Issue number1
DOIs
Publication statusPublished - 18 Jan 2018

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Tumors
Genes
Modulation
MicroRNAs
Phosphoric Monoester Hydrolases
PTEN Phosphohydrolase
Modulators
Neoplasms
Proteins
Chemical activation
Post Translational Protein Processing
Messenger RNA
Molecules
Therapeutics

Keywords

  • miR-21
  • new modalities
  • phosphatase
  • cancer
  • Neurodegenerative Diseases
  • anti-gene
  • anti-sense
  • gene editing
  • miRNA maturation
  • protein-protein interaction

VU Research Profile

  • Human Health and Life Sciences

Cite this

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title = "The Therapeutic Potential of PTEN Modulation: Targeting Strategies from Gene to Protein",
abstract = "Two decades have passed since the discovery of the tumor suppressor, PTEN. A multitude of biological functions have since been revealed, suggesting potential therapeutic applications for both PTEN activation (e.g., cancer) and inhibition (e.g., neuroregeneration). Nevertheless, PTEN's therapeutic suitability has been called into question due to its “risky” profile as a tumor suppressor. To evaluate PTEN function and its various roles in disease a number of molecules have so far been developed. However, intrinsic problems associated with phosphatase inhibition and PTEN's complex regulation via post-translational modifications hinder straightforward access to selective modulators. For this reason, central questions associated with PTEN targeting remain unanswered. In this perspective, we summarize current PTEN-targeting strategies and discuss potential approaches to modulate its functional dose, considering all stages of PTEN biogenesis from direct protein modulation to the targeting of relevant miRNAs as well as the PTEN gene and mRNA",
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The Therapeutic Potential of PTEN Modulation: Targeting Strategies from Gene to Protein. / McLoughlin, N.M.; Mueller, C.; Grossmann, T.N.

In: Cell Chemical Biology, Vol. 25, No. 1, 18.01.2018, p. 19-29.

Research output: Contribution to JournalReview articleAcademicpeer-review

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AU - McLoughlin, N.M.

AU - Mueller, C.

AU - Grossmann, T.N.

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N2 - Two decades have passed since the discovery of the tumor suppressor, PTEN. A multitude of biological functions have since been revealed, suggesting potential therapeutic applications for both PTEN activation (e.g., cancer) and inhibition (e.g., neuroregeneration). Nevertheless, PTEN's therapeutic suitability has been called into question due to its “risky” profile as a tumor suppressor. To evaluate PTEN function and its various roles in disease a number of molecules have so far been developed. However, intrinsic problems associated with phosphatase inhibition and PTEN's complex regulation via post-translational modifications hinder straightforward access to selective modulators. For this reason, central questions associated with PTEN targeting remain unanswered. In this perspective, we summarize current PTEN-targeting strategies and discuss potential approaches to modulate its functional dose, considering all stages of PTEN biogenesis from direct protein modulation to the targeting of relevant miRNAs as well as the PTEN gene and mRNA

AB - Two decades have passed since the discovery of the tumor suppressor, PTEN. A multitude of biological functions have since been revealed, suggesting potential therapeutic applications for both PTEN activation (e.g., cancer) and inhibition (e.g., neuroregeneration). Nevertheless, PTEN's therapeutic suitability has been called into question due to its “risky” profile as a tumor suppressor. To evaluate PTEN function and its various roles in disease a number of molecules have so far been developed. However, intrinsic problems associated with phosphatase inhibition and PTEN's complex regulation via post-translational modifications hinder straightforward access to selective modulators. For this reason, central questions associated with PTEN targeting remain unanswered. In this perspective, we summarize current PTEN-targeting strategies and discuss potential approaches to modulate its functional dose, considering all stages of PTEN biogenesis from direct protein modulation to the targeting of relevant miRNAs as well as the PTEN gene and mRNA

KW - miR-21

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KW - Neurodegenerative Diseases

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KW - anti-sense

KW - gene editing

KW - miRNA maturation

KW - protein-protein interaction

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