The Skp2 Pathway: A Critical Target for Cancer Therapy.

dc.contributor.author

Cai, Zhen

dc.contributor.author

Moten, Asad

dc.contributor.author

Peng, Danni

dc.contributor.author

Hsu, Che-Chia

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Pan, Bo-Syong

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Manne, Rajeshkumar

dc.contributor.author

Li, Hong-Yu

dc.contributor.author

Lin, Hui-Kuan

dc.date.accessioned

2024-06-10T19:51:45Z

dc.date.available

2024-06-10T19:51:45Z

dc.date.issued

2020-12

dc.description.abstract

Strictly regulated protein degradation by ubiquitin-proteasome system (UPS) is essential for various cellular processes whose dysregulation is linked to serious diseases including cancer. Skp2, a well characterized component of Skp2-SCF E3 ligase complex, is able to conjugate both K48-linked ubiquitin chains and K63-linked ubiquitin chains on its diverse substrates, inducing proteasome mediated proteolysis or modulating the function of tagged substrates respectively. Overexpression of Skp2 is observed in various human cancers associated with poor survival and adverse therapeutic outcomes, which in turn suggests that Skp2 engages in tumorigenic activity. To that end, the oncogenic properties of Skp2 are demonstrated by various genetic mouse models, highlighting the potential of Skp2 as a target for tackling cancer. In this article, we will describe the downstream substrates of Skp2 as well as upstream regulators for Skp2-SCF complex activity. We will further summarize the comprehensive oncogenic functions of Skp2 while describing diverse strategies and therapeutic platforms currently available for developing Skp2 inhibitors.

dc.identifier

S1044-579X(20)30012-2

dc.identifier.issn

1044-579X

dc.identifier.issn

1096-3650

dc.identifier.uri

https://hdl.handle.net/10161/31156

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Seminars in cancer biology

dc.relation.isversionof

10.1016/j.semcancer.2020.01.013

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Animals

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Humans

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Mice

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Neoplasms

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S-Phase Kinase-Associated Proteins

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Carcinogens

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Gene Expression Regulation

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Drug Resistance, Neoplasm

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Female

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Male

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Metabolic Networks and Pathways

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Ubiquitination

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Molecular Targeted Therapy

dc.title

The Skp2 Pathway: A Critical Target for Cancer Therapy.

dc.type

Journal article

duke.contributor.orcid

Hsu, Che-Chia|0000-0001-5630-5207

duke.contributor.orcid

Manne, Rajeshkumar|0000-0002-2393-1348

pubs.begin-page

16

pubs.end-page

33

pubs.issue

Pt 2

pubs.organisational-group

Duke

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School of Medicine

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Staff

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Pharmacology & Cancer Biology

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Pathology

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Duke Cancer Institute

pubs.publication-status

Published

pubs.volume

67

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