A novel mechanism for regulating the activity of proliferating cell nuclear antigen by a small protein

Li, Zhuo; Huang, Richard Y.-C.; Yopp, Daniel C.; Hileman, Travis H.; Santangelo, Thomas J.; Hurwitz, Jerard; Hudgens, Jeffrey W.; Kelman, Zvi

doi:10.1093/nar/gku239

i

A novel mechanism for regulating the activity of proliferating cell nuclear antigen by a small protein

Supporting Files

Apr 11 2014
By Li, Zhuo ; Huang, Richard Y.-C. ; Yopp, Daniel C.
http://dx.doi.org/10.1093/nar/gku239
Available in CDC Stacks on 2014-04-11T00:00:00Z

Details

Alternative Title:

Nucleic Acids Res
Personal Author:

Li, Zhuo ; Huang, Richard Y.-C. ; Yopp, Daniel C. ; Hileman, Travis H. ; Santangelo, Thomas J. ; Hurwitz, Jerard ; Hudgens, Jeffrey W. ; Kelman, Zvi
Description:

Proliferating cell nuclear antigen (PCNA) forms a trimeric ring that associates with and influences the activity of many proteins participating in DNA metabolic processes and cell cycle progression. Previously, an uncharacterized small protein, encoded by TK0808 in the archaeon Thermococcus kodakarensis, was shown to stably interact with PCNA in vivo. Here, we show that this protein, designated Thermococcales inhibitor of PCNA (TIP), binds to PCNA in vitro and inhibits PCNA-dependent activities likely by preventing PCNA trimerization. Using hydrogen/deuterium exchange mass spectrometry and site-directed mutagenesis, the interacting regions of PCNA and TIP were identified. Most proteins bind to PCNA via a PCNA-interacting peptide (PIP) motif that interacts with the inter domain connecting loop (IDCL) on PCNA. TIP, however, lacks any known PCNA-interacting motif, suggesting a new mechanism for PCNA binding and regulation of PCNA-dependent activities, which may support the development of a new subclass of therapeutic biomolecules for inhibiting PCNA.
Subjects:
Source:

Nucleic Acids Res. 2014; 42(9):5776-5789.
Pubmed ID:

24728986
Pubmed Central ID:

PMC4027161
Document Type:

Journal Article
Funding:

GH034559/GH/CGH CDC HHS/United States ; GM098176/GM/NIGMS NIH HHS/United States ; GM100329/GM/NIGMS NIH HHS/United States ; R01 GM100329/GM/NIGMS NIH HHS/United States
Volume:

42
Issue:

9
Download URL:

https://stacks.cdc.gov/view/cdc/32201/cdc_32201_DS1.pdf
File Type:

[PDF - 3.83 MB]
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:0458a572d7cd0e94b8d928c9f96dca35f681b65997779658b3c04842cea60c6f

ON THIS PAGE

Details Supporting Files

Was this page helpful?

Found an issue?

Send us an email at:

publishinghd@cdc.gov

CDC STACKS serves as an archival repository of CDC-published products including scientific findings, journal articles, guidelines, recommendations, or other public health information authored or co-authored by CDC or funded partners.

As a repository, CDC STACKS retains documents in their original published format to ensure public access to scientific information.