Characterization of the pVHL Interactome in Human Testis Using High-Throughput Library Screening

Functional impairment of the von Hippel-Lindau (pVHL) tumor suppressor is causative of a familiar increased risk to develop cancer. As E3 substrate recognition particle, pVHL marks for degradation the hypoxia inducible factor 1α (HIF-1α) in normoxic conditions, thus acting as a key regulator of both acute and chronic cell adaptation to hypoxia. Further evidence showed pVHL to also play relevant roles in microtubules stabilization, participate in the formation of the extracellular matrix, as well as to regulate cell senescence and apoptosis. Male mice model carrying VHL gene conditional knockout present significative abnormalities in testis development paired with defects in spermatogenesis and infertility, indicating that pVHL exerts testis-specific roles, at least in mice. Here, we describe 55 novel interactors of the human pVHL obtained by testis-tissue library screening. We show that pVHL interacts with multiple human proteins directly involved in spermatogenesis and reproductive metabolism, suggesting that, in addition to its role in cancer formation, pVHL may be pivotal in the correct gonads development also in human.