Polypeptide sequences enriched with proline (P), glutamic acid (E), aspartic acid (D) and serine (S)/ threonine (T) (PEST) have been reported to be the most abundant and frequently distributed at the cellular level. There is growing evidence that PEST sequences act as proteolytic recognition signals for degradation of residual proteins which is critical for activation or deactivation of regulatory proteins involved in cellular signaling pathways of cell growth, differentiation, stress responses and physiological death. A PEST containing nuclear protein (PCNP) was demonstrated as a tumor suppressor in a neuroblastoma cancer model and tumor promoter in lung adenocarcinoma cancer model. Its unique properties like ubiquitination by NIRF, co-localization with NIRF in nucleus and tumor progression attract the attention of researchers. PCNP was reported to be ubiquitinated by ring finger protein NIRF in E3 ligase manner and as modulator of MAPK and PI3K/AKT/mTOR signaling pathways. In this review, we summarize PCNP linked DNA damage response, Post translational modifications, and transportation to address initiation, prognosis, and resistance of tumor cells in terms of cell cycle regulation, transcription and apoptosis. Hence, we demonstrate PCNP as a novel target in cancer diagnosis and treatment.
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http://dx.doi.org/10.1002/cam4.2465 | DOI Listing |
T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers.
View Article and Find Full Text PDFPLoS Genet
January 2025
Center for Functional Genomics and Bioinformatics, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
A bidirectional nucleus-mitochondria communication is essential for homeostasis and stress. By acting as critical molecules, the nuclear-encoded lncRNAs (nulncRNAs) have been implicated in the nucleus-to-mitochondria anterograde regulation. However, role of mitochondrial-derived lncRNAs (mtlncRNAs) in the mitochondria-to-nucleus retrograde regulation remains elusive.
View Article and Find Full Text PDFPLoS Biol
January 2025
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada.
The role of epigenetics and chromatin in the maintenance of postmitotic neuronal cell identities is not well understood. Here, we show that the histone methyltransferase Trithorax (Trx) is required in postmitotic memory neurons of the Drosophila mushroom body (MB) to enable their capacity for long-term memory (LTM), but not short-term memory (STM). Using MB-specific RNA-, ChIP-, and ATAC-sequencing, we find that Trx maintains homeostatic expression of several non-canonical MB-enriched transcripts, including the orphan nuclear receptor Hr51, and the metabolic enzyme lactate dehydrogenase (Ldh).
View Article and Find Full Text PDFPLoS One
January 2025
Division of Oral Physiology, Faculty of Dentistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
This study examined the effects of treadmill running (TR) regimens on craniofacial pain- and anxiety-like behaviors, as well as their effects on neural changes in specific brain regions of male mice subjected to repeated social defeat stress (SDS) for 10 days. Behavioral and immunohistochemical experiments were conducted to evaluate the impact of TR regimens on SDS-related those behaviors, as well as epigenetic and neural activity markers in the anterior cingulate cortex (ACC), insular cortex (IC), rostral ventromedial medulla (RVM), and cervical spinal dorsal horn (C2). Behavioral responses were quantified using multiple tests, while immunohistochemistry measured histone H3 acetylation, histone deacetylases (HDAC1, HDAC2), and neural activity markers (FosB and phosphorylated cAMP response element-binding protein (pCREB).
View Article and Find Full Text PDFPLoS One
January 2025
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
Purpose: Rose Bengal Photodynamic Therapy (RB-PDT) offers dual therapeutic benefits by enhancing corneal stiffness and providing antibacterial activity, presenting significant potential for patients with keratoconus complicated by keratitis. Our purpose was to assess the effect of rose bengal photodynamic therapy (RB-PDT) on the expression of pro-inflammatory cytokines and chemokines, as well as on extracellular matrix (ECM)-related molecules, in lipopolysaccharide (LPS)-induced inflammation of keratoconus human corneal fibroblasts (KC-HCFs). Additionally, the involvement of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways which are downstream of the Toll-like receptor 4 (TLR4) pathway were examined.
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