Changes in intracellular calcium (Ca²⁺) levels serve to signal responses to diverse stimuli. Ca²⁺ signals are likely perceived through proteins that bind Ca²⁺, undergo conformation changes following Ca²⁺ binding, and interact with target proteins. The 50-member calmodulin-like (CML) Arabidopsis (Arabidopsis thaliana) family encodes proteins containing the predicted Ca²⁺-binding EF-hand motif. The functions of virtually all these proteins are unknown. CML24, also known as TCH2, shares over 40% amino acid sequence identity with calmodulin, has four EF hands, and undergoes Ca²⁺-dependent changes in hydrophobic interaction chromatography and migration rate through denaturing gel electrophoresis, indicating that CML24 binds Ca²⁺ and, as a consequence, undergoes conformational changes. CML24 expression occurs in all major organs, and transcript levels are increased from 2- to 15-fold in plants subjected to touch, darkness, heat, cold, hydrogen peroxide, abscisic acid (ABA), and indole-3-acetic acid. However, CML24 protein accumulation changes were not detectable. The putative CML24 regulatory region confers reporter expression at sites of predicted mechanical stress; in regions undergoing growth; in vascular tissues and various floral organs; and in stomata, trichomes, and hydathodes. CML24-underexpressing transgenics are resistant to ABA inhibition of germination and seedling growth, are defective in long-day induction of flowering, and have enhanced tolerance to CoCl₂, molybdic acid, ZnSO₄, and MgCl₂. MgCl₂ tolerance is not due to reduced uptake or to elevated Ca²⁺ accumulation. Together, these data present evidence that CML24, a gene expressed in diverse organs and responsive to diverse stimuli, encodes a potential Ca²⁺ sensor that may function to enable responses to ABA, daylength, and presence of various salts.

In plants, flowering is a critical developmental transition orchestrated by four regulatory pathways. Distinct alleles encoding mutant forms of the Arabidopsis potential calcium sensor CML24 cause ...

While meant for wound healing and immunity in response to injury and infection, inflammatory signaling is usurped by cancerous tumors to promote disease progression, including treatment resistance. The interleukin-1 (IL-1) inflammatory cytokine family functions in wound healing and innate and adaptive immunity. Two major, closely related IL-1 family members, IL-1α and IL-1β, promote tumorigenic phenotypes and contribute to treatment resistance in cancer. IL-1 signaling converges on transactivation of the Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP-1) transcription factors. NF-κB and AP-1 signaling are also activated by the inflammatory cytokine Tumor Necrosis Factor Alpha (TNFα) and microbe-sensing Toll-Like Receptors (TLRs). As reviewed elsewhere, IL-1, TNFα, and TLR can promote cancer progression through NF-κB or AP-1. In this review, we focus on what is known about the role of IL-1α and IL-1β in breast cancer (BCa) progression and therapeutic resistance, and state evidence for the role of NF-κB in mediating IL-1-induced BCa progression and therapeutic resistance. We will present evidence that IL-1 promotes BCa cell proliferation, BCa stem cell expansion, angiogenesis, and metastasis. IL-1 also regulates intracellular signaling and BCa cell hormone receptor expression in a manner that confers a growth advantage to the tumor cells and allows BCa cells to evade therapy. As such, the IL-1 receptor antagonist, anakinra, is in clinical trials to treat BCa and multiple other cancer types. This article presents a review of the literature from the 1990s to the present, outlining the evidence supporting a role for IL-1 and IL-1-NF-κB signaling in BCa progression.

Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and ad...