Journal of Preventive Medicine

The Cause of Severe Combined Immunodeficiency

Speckle-type pox virus and zinc finger protein (SPOP), a cullin-3/RING ubiquitin E3 complex substrate recognition receptor, ubiquitinate more than 40 of its target substrates. Due to the discovery of a variety of point mutations in the substrate-binding domain of SPOP in cancers, including endometrial and prostate cancers, the pathological roles of those cancer-associated SPOP mutants have been extensively elucidated. The function of the wild-type SPOP gene in non-cancerous human keratinocyte-derived HaCaT cells was the focus of this investigation. SPOP siRNA knockdown significantly slowed cell growth and stopped cell cycles at the G1/S phase in HaCaT cells. The DNA replication licensing factors CDT1 and CDC6's translation was stifled when SPOP was knocked out, which led to a significant decrease in their expression in HaCaT cells. Downregulation of CDT1 and CDC6 induced p21 expression without activating p53. SPOP is required for DNA replication licensing in non-cancerous keratinocyte HaCaT cells, as shown by our findings. Mutations in genes that play important roles in the development, maintenance, or function of the immune system are the cause of a diverse group of monogenic immunologic disorders known as inborn errors of immunity. A mutation in a gene that restricts immune cell expression or function is frequently the root cause of an immune disorder. However, several categories of immune inborn errors are brought on by mutations in genes that are expressed everywhere. Despite the fact that genes involved in cellular processes that are shared by all cell types are conserved, immune cells are disproportionately affected. Innate immune deficiencies are the result of this. Defects in the DNA repair machinery are known to be the cause of severe combined immunodeficiency in TBNK+. A brand-new class of inherited immune errors are DNA replication factor mutations.

Author(s): Tomas lee

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