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The N-terminal peptide of the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin determines substrate specificity

Kaldis, Philipp LU orcid (2005) In Journal of Biological Chemistry 280(12). p.11165-11174
Abstract

Cyclin-dependent kinases (Cdks) are activated by cyclin binding and phosphorylation by the Cdk-activating kinase (CAK). Activation of Cdk6 by the D-type cycling requires phosphorylation of Cdk6 by CAK on threonine 177. In contrast, Cdk6 is activated by the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin in the absence and presence of CAK phosphorylation. The activity of Cdk6·KSHV-cyclin complexes was investigated here by analyzing mutants of the KSHV-cyclin and Cdk6 in vitro as well as in U2OS cells. Deletion of the N terminus of the KSHV-cyclin affects the substrate specificity indicating that the N terminus is required for phosphorylation of histone H1 but not for other substrates. Mutation of residues in the region 180-200 of... (More)

Cyclin-dependent kinases (Cdks) are activated by cyclin binding and phosphorylation by the Cdk-activating kinase (CAK). Activation of Cdk6 by the D-type cycling requires phosphorylation of Cdk6 by CAK on threonine 177. In contrast, Cdk6 is activated by the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin in the absence and presence of CAK phosphorylation. The activity of Cdk6·KSHV-cyclin complexes was investigated here by analyzing mutants of the KSHV-cyclin and Cdk6 in vitro as well as in U2OS cells. Deletion of the N terminus of the KSHV-cyclin affects the substrate specificity indicating that the N terminus is required for phosphorylation of histone H1 but not for other substrates. Mutation of residues in the region 180-200 of the KSHV-cyclin decreases the binding affinity to Cdk6 in U2OS cells but increases the activity of Cdk6·KSHV-cyclin complexes in vitro indicating that low affinity binding of cyclins to the Cdk subunit might favor increased on- or off-rates of Cdk substrates. Expression of high levels of p16INK4ain cells leads to the formation of a heterotrimeric complex composed of Cdk6, KSHV-cyclin, and p16INK4a. Some of the Cdk6·KSHV-cyclin·p16 complexes were found to be active indicating that there might be different modes of p16 binding to Cdk6·cyclin complexes.

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author
publishing date
type
Contribution to journal
publication status
published
in
Journal of Biological Chemistry
volume
280
issue
12
pages
11165 - 11174
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:15664993
  • scopus:15744399579
ISSN
0021-9258
DOI
10.1074/jbc.M408887200
language
English
LU publication?
no
id
b9d1e8d1-bcc2-494c-8050-982c73e0d86c
date added to LUP
2019-09-18 14:28:11
date last changed
2024-05-14 23:08:29
@article{b9d1e8d1-bcc2-494c-8050-982c73e0d86c,
  abstract     = {{<p>Cyclin-dependent kinases (Cdks) are activated by cyclin binding and phosphorylation by the Cdk-activating kinase (CAK). Activation of Cdk6 by the D-type cycling requires phosphorylation of Cdk6 by CAK on threonine 177. In contrast, Cdk6 is activated by the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin in the absence and presence of CAK phosphorylation. The activity of Cdk6·KSHV-cyclin complexes was investigated here by analyzing mutants of the KSHV-cyclin and Cdk6 in vitro as well as in U2OS cells. Deletion of the N terminus of the KSHV-cyclin affects the substrate specificity indicating that the N terminus is required for phosphorylation of histone H1 but not for other substrates. Mutation of residues in the region 180-200 of the KSHV-cyclin decreases the binding affinity to Cdk6 in U2OS cells but increases the activity of Cdk6·KSHV-cyclin complexes in vitro indicating that low affinity binding of cyclins to the Cdk subunit might favor increased on- or off-rates of Cdk substrates. Expression of high levels of p16<sup>INK4a</sup>in cells leads to the formation of a heterotrimeric complex composed of Cdk6, KSHV-cyclin, and p16<sup>INK4a</sup>. Some of the Cdk6·KSHV-cyclin·p16 complexes were found to be active indicating that there might be different modes of p16 binding to Cdk6·cyclin complexes.</p>}},
  author       = {{Kaldis, Philipp}},
  issn         = {{0021-9258}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{12}},
  pages        = {{11165--11174}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{The N-terminal peptide of the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin determines substrate specificity}},
  url          = {{http://dx.doi.org/10.1074/jbc.M408887200}},
  doi          = {{10.1074/jbc.M408887200}},
  volume       = {{280}},
  year         = {{2005}},
}