Theology and organization

This Introduction argues for the importance of theology for the study of organization. It also draws the contours of a possible 'theology of organization'. Theology of organization, as we use it here, does not refer to a study of organization that is rooted in faith, nor does it refer to a study of religious practices in organizations. Instead, theology of organization recognizes that the way we think about and act in organizations is profoundly structured by theological concepts. In this editorial to the special issue we have three aims: to outline what theology of organization is, to show how it builds upon Carl Schmitt's 'political theology' and Giorgio Agamben's 'economic theology' and finally to propose three different forms that theology of organization can take. These forms of theology of organization respectively (1) analyse organizational concepts as secularized theological concepts, (2) show how theological concepts have survived unaltered in organizational contexts and (3) show how theological concepts have been corrupted or lost their original meaning when deployed in organizational contexts. In the final section of this editorial, we introduce the five contributions to this issue and indicate how they connect to the three forms of theology of organization that we have proposed

Covalent targeting of remote cysteine residues to develop CDK12 and 13 inhibitors

Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities