POGZ in autism and mitotic regulation

Intellectual disability (ID) and autism spectrum disorders (ASD) are genetically heterogeneous neurodevelopmental disorders with unclear etiology and pathogenesis. Genetic studies have identified de-novo mutated ASD-associated genes; however, the function of these de-novo mutated genes remains unclear. Studies from families affected by ASD and developmental delay (DD) have shown that POGZ is likely a risk gene for neurodevelopmental disorders. Recently, truncating mutations in POGZ have been reported among unrelated individuals. Although the phenotypes were variable, there is evidence of shared phenotypic features, suggesting that mutations in this gene might represent a distinct ASD and/or ID syndrome. POGZ encodes a heterochromatin protein 1 a-binding protein containing a cluster of multiple C2H2-type zinc fingers. POGZ is involved in mitosis and is expressed in the human fetal and adult brain. POGZ has an important role in mitosis, suggesting a possible role in regulating neuronal proliferation.

Here we focus on the mitotic regulation of POGZ and its interaction with the anaphase promoting complex/cyclosome (APC/C) inhibitor- MAD2L2. We present a clear mitotic behavior for POGZ. POGZ protein levels degraded upon release from mitosis, and accumulate again from mid S phase. We found that POGZ might be a substrate of the APC/C as its degradation is depended on the APC/C and proteasome. As POGZ binding to MAD2L2 was described only in MS, we aim to characterize their interaction using Co-IP. MAD2L2 and POGZ are important for mitotic regulation and understanding their mechanism of action will contribute in understanding the molecular basis for ASD and similar disorders.