HN1 Is Enriched in the S-Phase, Phosphorylated in Mitosis, and Contributes to Cyclin B1 Degradation in Prostate Cancer Cells

Abstract

HN1 has previously been shown as overexpressed in various cancers. In Prostate cancer, it regulates AR signaling and centrosome-related functions. Previously, in two different studies, HN1 expression has been observed as inversely correlated with Cyclin B1. However, HN1 interacting partners and the role of HN1 interactions in cell cycle pathways have not been completely elucidated. Therefore, we used Prostate cancer cell lines again and utilized both transient and stable inducible overexpression systems to delineate the role of HN1 in the cell cycle. HN1 characterization was performed using treatments of kinase inhibitors, western blotting, flow cytometry, immunofluorescence, cellular fractionation, and immunoprecipitation approaches. Our findings suggest that HN1 overexpression before mitosis (post-G2), using both transient and stable expression systems, leads to S-phase accumulation and causes early mitotic exit after post-G2 overexpression. Mechanistically, HN1 interacted with Cyclin B1 and increased its degradation via ubiquitination through stabilized Cdh1, which is a co-factor of the APC/C complex. Stably HN1-expressing cells exhibited a reduced Cdt1 loading onto chromatin, demonstrating an exit from a G1 to S phenotype. We found HN1 and Cdh1 interaction as a new regulator of the Cyclin B1/CDK1 axis in mitotic regulation which can be explored further to dissect the roles of HN1 in the cell cycle.

Matrine exerts an anti‐tumor effect via regulating HN1 in triple breast cancer both in vitro and in vivo

“…Hematological and neurological expression of 1 (HN1) gene, also named HN1A, ARM2, or JPT1, is located on chromosome 17q25.2 and encodes microtubule‐associated proteins of 16.5 kDa (Javed et al, 2023; Yin et al, 2020). It is up‐regulated in many cancers, and some evidence suggests that HN1 up‐regulates and controls its progression in some cancers, such as breast cancer (Morris et al, 2007) and liver cancer (Liu et al, 2020).…”

How the Timing of Biological Processes Is Controlled and Modified at the Molecular and Cellular Level? 2.0

“…Aadil Javed and colleagues [ 2 ] studied Hematological and Neurological Expressed 1 (HN1), which is the protein that has been previously shown to be especially highly expressed in prostate cancer cells. Its involvement in the cell cycle regulation was suggested due to a very specific pattern of expression: it is inversely correlated with cyclin B1 (the regulator of the major cell cycle kinase CDK1 or p34 cdc2 ).…”