Several studies have revealed that cyclin-dependent kinases (CDK) can mediate 
phosphorylation of steroid receptors at multiple sites, including serine 81 of 
the androgen receptor (AR). Phosphorylation of S81 is required for AR nuclear 
translocation, an association with chromatin and also regulates endogenous 
AR-regulated transcription in response to hormones. Up to date, 
S81-phosphorylation has been studied using different CDK inhibitors. 
Nevertheless, most inhibitors are non-selective or have unknown selectivity. We 
investigated the selectivity of commercially available CDK inhibitors and 
identified compounds that will be suitable for further studies to identify the 
CDKs responsible for S81-AR phosphorylation. We confirmed the positive impact of 
CDK1 and CDK9 on phosphorylation of S81-AR and its transcriptional activity. 
Although CDK1-mediated phosphorylation was previously shown to occur during 
mitosis, our experiments did not confirm this finding. By using chemical and 
genetic inhibition techniques, we identified that CDK2 contributes to S81-AR 
phosphorylation and transactivation while CDK4 was not shown to be involved in 
this process.