The phytohormone abscisic acid (ABA) triggers the activation of Snf1-related protein kinase 2s (SnRK2s) for adaptation to abiotic stress conditions. However, osmotic stress-induced ABA accumulation is slow while Ca2+ signals occur immediately. In this issue of Developmental Cell, Li et al. show that a subset of calcium-dependent kinases decode Ca2+ signals to directly control SnRK2 activation and thus

The hormone auxin regulates many aspects of plant growth and development. In a recent issue of Nature, Chen et al. report that an adenylate cyclase activity of auxin receptors promotes auxin-induced transcription activation. This suggests that the second messenger cAMP functions differently in plants than in other organisms.

In a recent issue of Science, Chen et al. and Lu et al. define a wheat immune module comprising tandem kinase (TK)-NLR protein pairs that recognize fungal effectors and activate defense responses. These findings reveal previously unknown immune signaling mechanisms and provide a foundation for engineering disease resistance through molecular breeding.

Phosphorylation regulates the transition between phases of the RNA polymerase II (RNAPII) transcription cycle. The elongation factor SPT5 is phosphorylated by the CDK9 kinase on a flexible linker and in C-terminal repeat 1 (CTR1) to regulate promoter-proximal pausing and termination. In this study, Sun and Fisher report that the C-terminal repeat 2 (CTR2) region in SPT5 is also phosphorylated by CDK9

Previous studies have developed an approach to derive midbrain dopaminergic neurons from human embryonic stem (hES) cells. Tabar et al. now use these cells in an open, phase 1 clinical trial aiming to treat Parkinson’s disease (PD). The authors primarily assessed the safety and tolerability of bilateral grafts of cryopreserved dopaminergic neuron progenitor cells into the putamen of individuals with

Treatments that aim to alleviate the symptoms of Parkinson’s disease (PD) are only effective at the early stages and eventually lead to complications. Sawamoto et al. conduct an open-label, phase 1/2 clinical trial to test induced pluripotent stem (iPS) cell-derived dopaminergic cells as a therapeutic approach for PD. The researchers bilaterally transplanted allogeneic iPS cell-derived dopaminergic

In this issue of Molecular Cell, Bobadilla Ugarte et al.1 show that ACE1, a Cas4-family nuclease, partners with prokaryotic Argonautes to generate guide DNAs, revealing a dedicated siDNA biogenesis pathway in cyanobacterial immune systems.

In this issue of Molecular Cell, Lu et al.1 report conserved global translation suppression by Prkra, also known as PACT in humans, in response to double-stranded RNA stimulation. Prkra directly binds to RNA and sequesters eIF2 complexes in a PKR-independent manner.

Ribosome biogenesis is a complex and error-prone process, necessitating quality control mechanisms to degrade defective pre-ribosomal intermediates. In this issue of Molecular Cell, Akers et al.1 report the identification of a previously uncharacterized quality control pathway named ribosome assembly surveillance pathway (RASP), which functions to eliminate aberrant "dead-end" pre-60S assembly intermediates

The function of the proteasome besides degrading protein remains enigmatic. Goldberg et al. demonstrate that proteasomes can process proteins into antimicrobial peptides (AMPs) to ward off bacterial infection,1 revealing a new function of proteasomes in innate immunity.

Uracil incorporation into DNA, as a result of nucleotide pool imbalances or cytosine deamination (e.g., through APOBEC3A/3B), can result in replication stress and is the most common source of mutations in cancer and aging. Despite the critical role of uracil in genome instability, cancer development, and cancer therapy, only now is there emerging data on its impact on fundamental processes such as

The regulation of RNA polymerase II (RNAPII) activity requires orchestrated responses among genomic regulatory sequences and an expansive set of proteins and protein complexes. Despite intense study over five decades, mechanistic insights continue to emerge. Within the past 10 years, live-cell imaging and single-cell transcriptomics experiments have yielded new information about enhancer-promoter communication

The highly conserved basement membrane protein collagen IV is stereotypically composed of two α1 subunits and one α2 subunit. In this issue, Srinivasan et al. (https://doi.org/10.1083/jcb.202412118) show that specific C. elegans basement membranes include collagen IV trimers with other compositions, suggesting a new diversity.

Repair of DNA double-strand breaks requires chromatin opening; however, the mechanisms involved were unclear. This work shows that sequential histone deamidation and acetylation modifications induce chromatin decompaction by reducing positive charge at the DNA–nucleosome interface.

A distinct population of adipose progenitor cells contributes to the accumulation of visceral white adipose tissue in middle-aged male mice.

BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, the ULK1 complex and nascent IM

The ATG9 transmembrane protein scrambles lipids to regulate phagophore formation during autophagy. Two recent studies from Peng et al. (https://doi.org/10.1083/jcb.202411092) and De Tito et al. (https://doi.org/10.1101/2024.07.23.604321) identify ATG9 as a conserved regulator of lysosome repair in Caenorhabditis elegans and human cells, but differences in repair mechanisms exist between these taxa

In this issue of Cancer Cell, Zhang et al. reveal that PAI-1-induced SFRP2high cancer-associated fibroblasts reduce the abscopal effect of radioimmunotherapy. Targeting PAI-1 or SFRP2 enhances T cell recruitment and prevents the formation of an immunosuppressive perivascular niche, improving radioimmunotherapy’s abscopal effect.

(Cancer Cell 40, 1044–1059.e1–e8; September 12, 2022)

(Cancer Cell 22, 91–105; July 10, 2012)

A 2012 study discovered that RNA–binding proteins are more numerous and diverse than previously thought, many having non-canonical RNA-binding domains.

During animal cell cytokinesis, active RhoA assembles actomyosin-based contractile rings that tend to close asymmetrically. Through imaging C. elegans zygotes, Lebedev et al. (https://doi.org/10.1083/jcb.202405182) reveal that the scaffold protein, anillin, promotes asymmetric ring closure by locally sequestering RhoA from its canonical effectors and thereby limiting actomyosin contractility.

Cytokinesis, the final stage of cell division, serves to physically separate daughter cells. In cultured naïve mouse embryonic stem cells, cytokinesis lasts unusually long. Here, we describe a novel function for the kinesin-13 member KIF2A in this process. In genome-engineered mouse embryonic stem cells, we find that KIF2A localizes to spindle poles during metaphase and regulates spindle length in

Neurons release neurotransmitters from synaptic vesicles (SVs) and neuropeptides from dense-core vesicles (DCVs). The presynaptic proteins RIM and MUNC13 play key roles in both pathways. It remains unclear how DCVs are targeted to release sites and whether RIM and MUNC13 are involved in this process. Here, we show that three membrane-binding domains in RIM and MUNC13 regulate DCV exocytosis differently

(Developmental Cell 19, 259–269; August 17, 2010)

(Cell Stem Cell 29, 1459–1474.e1–e9; October 6, 2022)

In this issue, Jaffray and colleagues (https://doi.org/10.1083/jcb.202407133) detail the molecular machinery required to degrade the oncogene PML in response to arsenic treatment. Different posttranslational modifiers team up: ubiquitin, SUMO1, and -2/3, linked by the SUMO-targeted ubiquitin ligases TOPORS and RNF4.

The mechanisms governing the progression of precursor lesions to invasive lung adenocarcinoma (LUAD) remain poorly understood. In this issue of Cancer Cell, Zhu et al. map the dynamic immune changes associated with this progression using high-resolution spatial mapping. Their identification of TIM-3 as a potential target may shift strategies for LUAD immunoprevention.

Tumor-associated macrophages (TAMs) are key players in tumor progression, yet their role in this process remains only partially understood. In this issue of Cancer Cell, Sheban et al. demonstrate that zinc finger E-box-binding homeobox 2 (ZEB2) acts as a master regulator that reprograms TAMs toward a pro-tumor phenotype and that therapeutic targeting of ZEB2 exhibits anti-tumor activity.

Despite recent advances in anti-cancer therapies, metastasis, especially to the brain, represents a major clinical challenge with rising incidences. In this issue of Cancer Cell, Xing et al. present a comprehensive transcriptomic map of the metastatic brain tumor environment at single-cell resolution.