VCP promotes tTAF-target gene expression and spermatocyte differentiation by downregulating mono-ubiquitylated H2A.

ABSTRACT: Valosin-containing protein (VCP) binds and extracts ubiquitylated cargo to regulate protein homeostasis. VCP has been studied primarily in aging and disease contexts, but it also affects germline development. However, the precise molecular functions of VCP in the germline, particularly in males, are poorly understood. Using the Drosophila male germline as a model system, we find that VCP translocates from the cytosol to the nucleus as germ cells transition into the meiotic spermatocyte stage. Importantly, nuclear translocation of VCP appears to be one crucial event stimulated by testis-specific TBP-associated factors (tTAFs) to drive spermatocyte differentiation. VCP promotes the expression of several tTAF-target genes, and VCP knockdown, like tTAF loss of function, causes cells to arrest

SUBMITTER: Butsch TJ 

PROVIDER: S-EPMC10399981 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature