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Gene & Protein in Disease                                             β-cell regeneration and stem cell niche















































            Figure 7. Targeted inhibitors and important signaling pathways that regulate cancer stem cells. The Notch intracellular domain (NICD), which interacts
            with the transcription complex to promote gene expression, is released as part of the Notch pathway. The Dishevelled protein (DVL) is activated by the
            Wnt pathway, leading to the breakdown and accumulation of β-catenin in the cytoplasm. The Hedgehog (Hh) pathway entails the binding of Hh to patched
            (PTCH), the translocation of smoothened (SMO) to the cell membrane, and the release of GLIa, which triggers the transcription of downstream target
            genes. Reprinted from Ju et al. 30
            Abbreviations: APC: Adenomatous polyposis coli; CBP: CREB-binding protein; COS2: Costal2; CSL: CBF1, suppressor of hairless, Lag-1; DKK1:; GLI:
            Glioma-associated oncogene; GLIa: Glioma-associated oncogene a; MAML: Mastermind-like proteins; SKIP: ski-interacting protein; SUFU: Suppressor of
            Fused homolog; TCF/LEF: T-cell factor/lymphoid enhancer factor.

            interventions through both discovery and repurposing   fate. A ubiquitous biological mechanism known as protein
            initiatives, developing chemical compounds targeting   phosphorylation enables the regulation of protein activity
            classes B2 and F GPCRs to address unmet medical needs,   in a complex and reversible manner. Protein phosphatase
            and validating polypharmacology for enhanced drug   2A (PP2A), a heterotrimeric serine-threonine phosphatase
            treatments.                                        comprising structural, catalytic, and regulatory subunits,
              According to contemporary studies in stem cell   regulates several cellular processes by dephosphorylating
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            biology, the topography and viscoelasticity of the   proteins.  While the fundamental biochemistry of PP2A
            extracellular matrix, in particular, exert a substantial   is well understood, its precise function is challenging to
            influence on various aspects of stem cell behavior, such as   discern due to the diversity of its components, particularly
            self-renewal capacity and differentiation (Figure  9). The   the multitude of regulatory subunits. This complexity
            mechanical characteristics of stem cells play a crucial role   leads to PP2A’s dual regulation of signaling networks,
            in  maintaining  their  attachment  to  the  physical  milieu,   such as the Wnt pathway, which exhibits both positive and
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            thereby preserving their quiescence and hematopoietic   negative effects.  Wnt signaling is crucial in determining
            regeneration.  Both intrinsic and extrinsic mechanical   stem cell fate, self-renewal, and the formation of cancer
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            features are pivotal in regulating stem cell activity and   stem cells. Research in this area is advancing to deepen

            Volume 3 Issue 2 (2024)                         9                               doi: 10.36922/gpd.2996
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