Exploring the roles of CASK and calcium signalling in apoptosis-induced proliferation

Haque, Md. Iqramul (2024). Exploring the roles of CASK and calcium signalling in apoptosis-induced proliferation. University of Birmingham. Ph.D.

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Abstract

Apoptosis is one of the most characterised forms of programmed cell death, heavily reliant on caspases. Interestingly, many non-apoptotic functions of caspases have been reported recently. Among these functions is their capacity to elicit proliferation in neighbouring cells upon activation in stress or damaged cells, giving rise to a phenomenon known as apoptosis-induced proliferation (AiP) which is relevant to regeneration and tumourigenesis. The elucidation of regulatory mechanisms governing AiP has greatly benefited from studies conducted on the model organism Drosophila melanogaster. Notably, Dronc, an orthologue of the mammalian caspase-9, plays a pivotal role in activating the c-Jun N-terminal kinase (JNK) pathway, which leads to the release of multiple mitogenic factors including the Wnt orthologue Wingless (Wg), the TGF-β orthologue Decapentaplegic (Dpp) and the EGF orthologue Spitz (Spi), facilitating growth in the surrounding tissue. However, our knowledge of the molecular mechanisms underlying AiP remains quite limited. Recent work on AiP regulation has revealed F-actin polymerisation as a key event for the activation of JNK downstream of Dronc. In this PhD project, I have discovered a novel role of Calcium-calmodulin dependent serine protein kinase (CASK), a multidomain scaffold protein, in mediating F-actin polymerisation hence regulating AiP. Additionally, I have identified its potential interacting partners that have crucial roles in this process. Furthermore, I have explored the roles of calcium signalling in this process. Therefore, this study has unveiled novel functions of CASK, CASK-interacting proteins, and calcium signalling in the regulation of F-actin dynamics required for AiP.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):