Apoptosis is a cell death program that is executed by the caspases, a family of cysteine proteases that typically cleave after aspartate residues during a proteolytic cascade that systematically dismantles the dying cell. Extensive signaling crosstalk occurs between caspase-mediated proteolysis and kinase-mediated phosphorylation, enabling integration of signals from multiple pathways into the decision to commit to apoptosis. A new study from Maluch et al. examines how phosphorylation within caspase cleavage sites impacts the efficiency of substrate cleavage. The results demonstrate that while phosphorylation in close proximity to the scissile bond is generally inhibitory, it does not necessarily abrogate substrate cleavage, but instead attenuates the rate. In some cases, this inhibition can be overcome by additional favorable substrate features. These findings suggest potential nuanced physiological roles for phosphorylation of caspase substrates with exciting implications for targeting caspases with chemical probes and therapeutics.

中文翻译：

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激酶在半胱天冬酶底物上留下印记

细胞凋亡是由半胱天冬酶执行的细胞死亡程序，半胱氨酸蛋白酶家族通常在蛋白水解级联反应期间在天冬氨酸残基后裂解，系统性地分解垂死细胞。在半胱天冬酶介导的蛋白水解和激酶介导的磷酸化之间发生广泛的信号串扰，从而能够将来自多个途径的信号整合到细胞凋亡的决定中。Maluch 等人的一项新研究。检查 caspase 裂解位点内的磷酸化如何影响底物裂解的效率。结果表明，虽然靠近易裂键的磷酸化通常是抑制性的，但它不一定会消除底物裂解，而是会降低速率。在某些情况下，这种抑制可以通过额外的有利底物特征来克服。