Disease relevance of CCNK

• Using cDNA microarray technology, we found that cyclin K mRNA was dramatically increased in U373MG, a glioblastoma cell line deficient in wild-type p53, in the presence of exogenous p53 [1].
• Altogether, these results suggest that KSHV is able to override growth suppressive effects through multiple mechanisms, and they further indicate that cyclin K plays an important role in the oncogenic activity of these viruses [2].
• The primers CPL1 and CPR4 were tested for their ability to amplify DNA from 30 strains of C. neoformans and 27 specimens of cerebrospinal fluid (CSF) from patients with cryptococcal meningitis [3].

High impact information on CCNK

• Cyclin K was found to associate with the activation domain of STAT3 to inhibit its DNA-binding and transcriptional activities [2].
• The Kaposi sarcoma-associated human herpesvirus 8 (KSHV) encodes a protein, cyclin K, that is similar to cellular cyclin D1 but behaves atypically [2].
• Kaposi sarcoma-associated viral cyclin K overrides cell growth inhibition mediated by oncostatin M through STAT3 inhibition [2].
• Cyclin K mRNA is ubiquitously expressed in adult mouse and human tissues, but is most abundant in the developing germ cells of the adult testis and ovaries [4].
• P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA [5].

Biological context of CCNK

• A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the cell-cycle inhibitor p27(Kip1) [6].
• Cdk9 function depends on its kinase activity and also on its regulatory units: the T-family cyclins and cyclin K. Recently, several studies confirmed the role of cdk9 in different cellular processes such as signal transduction, basal transcription, HIV-Tat- and MyoD-mediated transcription and differentiation [7].
• We identified two other genes whose levels were decreased and these are known to be involved in the regulation of cell proliferation (cyclin K and p-100) [8].

Physical interactions of CCNK

• Modeling of CDK9 bound to cyclin K provides insights into the structural determinants underlying the formation and regulation of this complex [6].
• An electrophoretic mobility-shift assay showed that a potential p53-binding site (p53BS) in intron 1 of the cyclin K gene could indeed bind to p53 protein [1].

Regulatory relationships of CCNK

• The results suggested that cyclin K may play a role in regulating the cell cycle or apoptosis after being targeted for transcription by p53 [1].

Other interactions of CCNK

• The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box [6].
• Biochemical analyses indicate that cyclin K functions as a regulatory subunit of CDK9 [9].
• Cyclin K as a direct transcriptional target of the p53 tumor suppressor [1].
• Cyclin K, a newly recognized member of the "transcription" cyclin family, may play a dual role by regulating CDK and transcription [1].

Analytical, diagnostic and therapeutic context of CCNK

• In this study, we show that cyclin K overrides growth suppressive signals through signal transducer and activator of transcription 3 (STAT3) inactivation [2].

References