Arabidopsis RabGDIs mediate Rab targeting and are crucial for male gametophytic function.

Rab GTPases are key regulators of vesicular trafficking, not only switching between active and inactive forms but also cycling between donor/resident and target membranes, a process regulated by factors including guanine nucleotide dissociation inhibitors (RabGDIs), whose function is largely unknown in plants. By reverse genetic approaches, we demonstrate that Arabidopsis RabGDIs redundantly mediate male fertility such that the functional loss of RabGDIs compromises pollen development, germination, and directional growth of pollen tubes. By combining cellular and pharmacological approaches, we demonstrate that RabGDIs are critical for the targeting of Rab GTPases not only in secretory but also in vacuolar pathways.

Protein S-acylation, a new panacea for plant fitness.

Protein S-acylation or palmitoylation is a reversible post-translational modification that influences many proteins encoded in plant genomes. Exciting progress in the past 3 years demonstrates that S-acylation modulates subcellular localization, interacting profiles, activity, or turnover of substrate proteins in plants, participating in developmental processes and responses to abiotic or biotic stresses. In this review, we summarize and discuss the role of S-acylation in the targeting of substrate proteins.

S-acylation of YKT61 modulates its unconventional participation in the formation of SNARE complexes in Arabidopsis.

Hetero-tetrameric soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complexes are critical for vesicle-target membrane fusion within the endomembrane system of eukaryotic cells. SNARE assembly involves four different SNARE motifs, Qa, Qb, Qc, and R, provided by three or four SNARE proteins. YKT6 is an atypical R-SNARE that lacks a transmembrane domain and is involved in multiple vesicle-target membrane fusions.

Arabidopsis protein -acyl transferases positively mediate BR signaling through -acylation of BSK1.

Protein -acyl transferases (PATs) catalyze -acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially -acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through -acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1).

The landscape of systemic therapy for early stage triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with higher risk of disease recurrence and mortality than other breast cancer subtypes. Historically, chemotherapy has been the primary systemic treatment for early stage TNBC. Recent developments in immune checkpoint inhibitors (ICIs) and novel therapeutic agents have transformed the treatment of TNBC.

Hyperpatulones C-G, new spirocyclic polycyclic polyprenylated acylphloroglucinols from the leaves of Hypericum patulum.

Five new spirocyclic polycyclic polyprenylated acylphloroglucinols, Hyperpatulones C-G (1-5), were obtained from the leaves of Hypericum patulum. Their structures were characterized by the comprehensive analysis of their IR, NMR, CD spectra and HRESIMS data. All the new compounds were evaluated for the α-glycosidase inhibitory activities.

Misshapen Disruption Cooperates with to Drive Tumorigenesis.

Although family genes play essential roles in tumorigenesis, effective treatments targeting -related tumors are lacking, partly because of an incomplete understanding of the complex signaling crosstalk within -related tumors. Here, we performed a large-scale genetic screen in eye imaginal discs and identified () as a tumor suppressor that synergizes with oncogenic () to induce c-Jun N-terminal kinase (JNK) activation and Hippo inactivation, then subsequently leads to tumor overgrowth and invasion. Moreover, ectopic Msn expression activates Hippo signaling pathway and suppresses Hippo signaling disruption-induced overgrowth.

Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance.

Oncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear.

A novel regulator of ER Ca drives Hippo-mediated tumorigenesis.

Calcium ion (Ca) is a versatile second messenger that regulates various cellular and physiological functions. However, the in vivo molecular mechanisms by which Ca alterations contribute to tumor growth remain poorly explored. Here we show that Emei is a novel ER Ca regulator that synergizes with Ras to induce tumor growth via JNK-mediated Hippo signaling.

Mutations in the tricellular junction protein M6 synergize with to induce apical cell delamination and invasion.

Complications from metastasis are responsible for the majority of cancer-related deaths. Despite the outsized medical impact of metastasis, remarkably little is known about one of the key early steps of metastasis: departure of a tumor cell from its originating tissue. It is well documented that cellular delamination in the basal direction can induce invasive behaviors, but it remains unknown if apical cell delamination can induce migration and invasion in a cancer context.

PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion.

RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed, partly because of an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (Ras) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with Ras to drive c-Jun N-terminal kinase (JNK)-dependent tumor growth and invasiveness.

AUF1 is involved in splenic follicular B cell maintenance.

Background: The adenosine/uridine-rich element (ARE)-binding protein AUF1 functions to regulate the inflammatory response through the targeted degradation of cytokine and other mRNAs that contain specific AREs in their 3' noncoding region (3' NCR). To investigate the role of AUF1 in the immune system, we characterized the lymphoid compartments of AUF1-deficient mice.

Results: Mice lacking AUF1 exhibit an altered proportion and size of splenic B cell subsets.

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs.

Excessive production of proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), plays a critical role in septic shock induced by bacterial endotoxin (endotoxemia). Precise control of cytokine expression depends on rapid degradation of cytokine mRNAs, mediated by an AU-rich element (ARE) in the 3' noncoding region and by interacting ARE-binding proteins, which control the systemic inflammatory response. To understand the function of the ARE-binding protein AUF1, we developed an AUF1 knockout mouse.

Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay.

An AU-rich element (ARE) located in the 3'-untranslated region of many short-lived mRNAs functions as an instability determinant for these transcripts. AUF1/hnRNP D, an ARE-binding protein family consisting of four isoforms, promotes rapid decay of ARE-mRNAs. The mechanism by which AUF1 promotes rapid decay of ARE-mRNA is unclear.

Clinical manifestations and significance of post-traumatic thoracolumbar syringomyelia.

Objective: To analyze the pathogenic mechanism and the clinical significance of post-traumatic thoracolumbar syringomyelia through reviewing the clinical manifestations.

Methods: The data of 15 patients (14 males and 1 female, aged from 28 to 56 years, with an average of 36 years) with post-traumatic syringomyelia treated in our hospital from December 1997 to February 2002 were studied retrospectively. Two patients suffered from T11 fractures, 7 from T12 fractures and 6 from L1 fractures.

Tissue distribution of AU-rich mRNA-binding proteins involved in regulation of mRNA decay.

Short lived cytokine and proto-oncogene mRNAs are destabilized by an A+U-rich element (ARE) in the 3'-untranslated region. Several regulatory proteins bind to AREs in cytokine and proto-oncogene mRNAs, participate in inhibiting or promoting their rapid degradation of ARE mRNAs, and influence cytokine expression and cellular transformation in experimental models. The tissue distribution and cellular localization of the different AU-rich binding proteins (AUBPs), however, have not been uniformly characterized in the mouse, a model for ARE mRNA decay.

Nuclear import and export functions in the different isoforms of the AUF1/heterogeneous nuclear ribonucleoprotein protein family.

The heterogeneous nuclear ribonucleoprotein D family of proteins also known as AUF1 consists of four isoforms implicated in both nuclear and cytoplasmic functions. The AUF1 proteins are largely nuclear but also are found in the cytoplasm and are thought to undergo nucleocytoplasmic shuttling. The nucleocytoplasmic distribution and potential shuttling activity of the individual AUF1 isoforms have not been previously studied in detail.