The N-terminal peptide of the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin determines substrate specificity
(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.
(Less)
- author
- Kaldis, Philipp
LU
- publishing date
- 2005-03-25
- 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}}, }