Determination of key components in the Bombyx mori p53 apoptosis regulation network using Y2H-Seq

Authors: WANG, MEIXIAN - Jiangsu University; WANG, JIAHAO - Jiangsu University; YASEN, AYINUER - Jiangsu University; FAN, BINGYAN - Jiangsu University; Hull, Joe; SHEN, XINGJIA - Jiangsu University

Submitted to: Insects
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/4/2023
Publication Date: 4/5/2023
Citation: Wang, M., Wang, J., Yasen, A., Fan, B., Hull, J.J., Shen, X. 2023. Determination of key components in the Bombyx mori p53 apoptosis regulation network using Y2H-Seq. Insects. 14(4). Article 362. https://doi.org/10.3390/insects14040362.
DOI: https://doi.org/10.3390/insects14040362

Interpretive Summary: Apoptosis is a highly regulated form of programmed cell death that plays a fundamental role in the removal of damaged cells and tissue remodeling during morphogenesis. For insects, this includes the significant changes in body planning associated with metamorphosis. Although apoptosis pathways are typically well-conserved across species, the presence of key regulatory genes and their associated protein networks remain to be fully characterized in many insect species beyond fruitflies. As a species that undergoes complete metamorphosis, the domesticated silkworm can be a model system for studying the regulation of apoptosis. Targeted disruption and overexpression of p53, a key apoptosis regulator in vertebrates, revealed a similar role in silkworms as evidenced by an induction of cellular apoptosis in cultured cells and impaired metamorphosis at the larval-pupae transition. A yeast two-hybrid based search of proteins that interact with the silkworm p53 homolog (Bmp53) identified a number of proteins that potentially regulate the pathways underlying apoptosis. One such protein termed MDM2-like, which may impact cellular ubiquitination, appears to be unique to silkworms. However, other proteins appear to be present in the genomes of other lepidopteran species. Consequently, functional analysis of the proteins that comprise the silkworm p53 regulatory network may provide insights into the regulation of apoptosis in other species. As such, further study has the potential to identify candidate metamorphosis-associated genes for novel targeted disruption control strategies.

Technical Abstract: The apoptosis pathway is highly conserved between invertebrates and mammals. Although genes encoding the classical apoptosis pathway can be found in the silkworm genome, the regulatory pathway and other apoptotic network genes have yet to be confirmed. Consequently, characterizing these genes and their underlying mechanisms could provide critical insights into the molecular basis of organ apoptosis and remodeling. A homolog of p53, a key apoptosis regulator in vertebrates, has been identified and cloned from Bombyx mori (Bmp53). This study confirmed via gene knockdown and overexpression that Bmp53 directly induces cell apoptosis and regulates the morphology and development of individuals during the metamorphosis stage. Furthermore, yeast two-hybrid sequencing (Y2H-Seq) identified several potential apoptotic regulatory interacting proteins, including the MDM2-like ubiquitination regulatory protein, which may represent an apoptosis factor unique to Bmp53 and which differs from that in other Lepidoptera. These results provide a theoretical basis for analyzing the various biological processes regulated by Bmp53 interaction groups and thus provide insight into the regulation of apoptosis in silkworms. The global interaction set identified in this study also provides a basic framework for future studies on apoptosis-dependent pupation in Lepidoptera.