Page 104 - MI-2-2

Microbes & Immunity Big data and DNN-based DTI model in CHP

typically promotes apoptosis and stress responses through degradation of mitotic cyclins and other proteins, allowing
JNK and p38α/β in MAPK. In contrast, AKT activation the cell to exit mitosis and enter the G1 phase. While not
64
promotes cell survival and growth, also controlling a direct substrate of CDH1, the regulation of CDK activity
gene expression related to apoptosis, survival, and by CDH1 indirectly affects CDC25A function. Proper
65
inflammation. JNK phosphorylates TF c-Jun, a major degradation of cyclins and other regulators ensures that
component of AP1. Phosphorylation increases c-Jun’s CDKs are only activated by CDC25A at the appropriate
58
transcriptional activity, enhancing AP1-mediated gene time. This process can inhibit CDC25A, preventing
expression. While TF JunD is less responsive to JNK the activation of CDKs and halt cell cycle progression.
59
phosphorylation compared to TF c-Jun, it can still Simultaneously, these checkpoints can influence the
participate in AP1 complexes regulated by JNK activity. activity of CDH1 to ensure that mitotic regulators are
Moreover, JNK stress-induced signals that activate JNK can properly degraded. Subsequently, CDC25A removes
64
enhance the transcriptional activity of AP1 components inhibitory phosphates from threonine-14 and tyrosine-15
that incorporate TF JunD, thereby influencing regulated on CDK2. This dephosphorylation is necessary for the
65
target genes NFAT/AP1. The NFAT-AP1-JNK axis plays activation of the CDK2/cyclin complexes, which also
60
a critical role in T-cell activation and differentiation. promotes the initiation of DNA replication, and ensures
The integration of signals from these pathways ensures proper cell cycle progression and genomic stability.
the proper transcriptional regulation of cytokines and CDK2 activity ensures proper DNA replication, while
other immune-related genes. The activation of target CDC20 regulates the exit from mitosis, ensuring that cells
gene AP1 by JNK in response to stress can lead to the only progress through the cell cycle when all necessary
expression of inflammation and apoptosis. This response conditions are met. Once CDC20 ubiquitinates Securin,
66
is modulated by the interaction with NFAT, allowing for the degradation of Securin releases the enzyme separase
61
a balanced cellular reaction to stress. Consequently, from its inhibition. Active separase can then cleave cohesin
CXCL1 activation subsequently induces the expression complexes, allowing the sister chromatids to separate
of pro-inflammatory genes, including CXCR2 ligands, and ensure proper cell division. During interphase and
and promotes cancer cell migration. CXCL1 can activate early mitosis, Securin binds to separase and inhibits its
these small GTPases through the PI3K pathway, initiating protease activity. This binding prevents separase from
63
downstream signaling events, such as the activation of p38 cleaving cohesin complexes that hold sister chromatids
MAPK and PAKs. 62 together. 63 Sep arase is activated at the onset of anaphase
In summary, the CXCL1 chemokine represents a and cleaves the cohesin complex to allow chromosome
network of proteins in Figure 4 that interacts with genes segregation, while STAG3-containing cohesin complexes
NFAT2, NFAT4, and AP1, and TF JunD through JNK maintain the cohesion of sister chromatids during the
signals that orchestrate various downstream signaling early stages of meiosis, ensuring proper alignment and
pathways, including those involved in chemotaxis, recombination. Abnormal expression of target gene STAG3
inflammation, and cancer cell migration. Elucidating the in somatic cells can interfere with the normal cohesin
66
intricate interplay within this chemo synapse is crucial for complex function, potentially affecting cell proliferation.
understanding the multifaceted roles of receptor CXCR2 Therefore, in vitro cell experiments have shown that
in physiological and pathological processes. CDC23 can promote the proliferation of myogenic cells
and significantly upregulate the differentiation of skeletal
3.3.2. The role of cell division cycle 23 in cell cycle muscle satellite cells. The PPI network shows a high level of
regulation and potential implications in CHP interaction between CDC23 and cell cycle pathway-related
Cell division cycle 23 is a component of the genes like STAG3. Subsequently, in CDC23-overexpressed
tetratricopeptide repeat (TPR) subunits in the anaphase- differentiated myogenic cells, the level of CDC23 was
promoting complex/cyclosome (APC/C) complex, significantly negatively correlated with the expression
involved in regulating mitosis in eukaryotes. Receptor of key factors in the cell cycle pathway, suggesting that
63
cyclin-dependent kinase 1 (CDK1) not only regulates CDC23 may be involved in inhibiting cell cycle signaling
the timing of APC/C activation to ensure proper mitotic pathways, thereby promoting differentiation.
entry, progression, and exit but also controls the initiation The APC/C, through CDC23 and other components,
of mitosis, whereas cadherin-1 (CDH1) regulates regulates the cell cycle, ensuring proper cell division and
the exit from mitosis and the maintenance of the G1 function. Dysregulation in cell cycle control can influence
phase (cell cycle). In late mitosis and G1 phase, CDH1 immune cell proliferation and function, potentially
becomes dephosphorylated and can bind to APC/C, impacting the inflammatory and immune responses
thereby activating it. This leads to the ubiquitination and seen in CHP. Compared to control cells, CDC23,

Volume 2 Issue 2 (2025) 96 doi: 10.36922/mi.4620