CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse

<div><p><i>Cyclin Y-like 1</i> (<i>Ccnyl1</i>) is a newly-identified member of the cyclin family and is highly similar in protein sequences to <i>Cyclin Y</i> (<i>Ccny</i>). However, the function of <i>Ccnyl1</i> is poorly characterized in any organism. Here we found that <i>Ccnyl1</i> was most abundantly expressed in the testis of mice and was about seven times higher than the level of <i>Ccny</i>. Male <i>Ccnyl1</i>-/- mice were infertile, whereas both male and female <i>Ccny</i>-/- mice displayed normal fertility. These results suggest that <i>Ccnyl1</i>, but not <i>Ccny</i>, is indispensable for male fertility. Spermatozoa obtained from <i>Ccnyl1</i>-/- mice displayed significantly impaired motility, and represented a thinned annulus region and/or a bent head. We found that the protein, but not the mRNA, level of cyclin-dependent kinase 16 (CDK16) was decreased in the testis of <i>Ccnyl1</i>-/- mice. Further study demonstrated that CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins. Moreover, the interaction increased the kinase activity of CDK16. In addition, we observed an alteration of phosphorylation levels of CDK16 in the presence of CCNYL1. We identified the phosphorylation sites of CDK16 by mass spectrometry and revealed that several phosphorylation modifications on the N-terminal region of CDK16 were indispensable for the CCNYL1 binding and the modulation of CDK16 kinase activity. Our results therefore reveal a previously unrecognized role of CCNYL1 in regulating spermatogenesis through the interaction and modulation of CDK16.</p>