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The zinc-responsive transcription activator Zap1 plays a central role in zinc homeostasis in the budding yeast Saccharomyces cerevisiae. In zinc-deficient cells, Zap1 binds to zinc responsive elements in target gene promoters and activates gene expression. In most cases, Zap1-dependent gene activation results in increased levels of mRNAs and proteins. However, Zap1-dependent activation of RTC4 results in increased levels of the RTC4 mRNA and decreased levels of the Rtc4 protein. This atypical regulation results from Zap1-mediated changes in the transcriptional start site for RTC4 and the production of a RTC4 transcript with a longer 5' leader. This long RTC4 transcript contains small upstream open reading frames that prevent translation of the downstream RTC4 ORF. The new studies with Zap1 highlight how a transcriptional activator can facilitate decreased protein expression.
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http://dx.doi.org/10.1111/mmi.13856 | DOI Listing |
Acta Neuropathol Commun
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Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFLab Anim Res
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Department of Pathology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Background: Stroke-prone spontaneously hypertensive rats (SHRSP) exhibit slow-twitch muscle-specific hypotrophy compared with normotensive Wistar-Kyoto rats (WKY). Because slow-twitch muscles are prone to disuse atrophy, SHRSP may experience both disuse atrophy and impaired recovery from it. This study investigated the response of SHRSP to disuse atrophy and subsequent recovery, using WKY as a control.
View Article and Find Full Text PDFCancer Immunol Immunother
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Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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Graduate Institute of Physiology, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan, Republic of China.
Peroxisome proliferator-activated receptor alpha (PPARα) is a crucial transcriptional factor that regulates fatty acid β-oxidation and ketogenesis in response to fasting. However, the mechanisms underlying PPARα function remain unclear. This study identified a novel PPARα-binding protein-RING finger protein 128 (RNF128)-that facilitates PPARα polyubiquitination, resulting in the degradation and suppression of PPARα function during fasting.
View Article and Find Full Text PDFActa Pharmacol Sin
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Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
The anti-HER2 antibody‒drug conjugate (ADC) DS-8201 presents new hope for patients with advanced HER2-positive tumors. Its clinical application, however, is hindered by serious adverse reactions and reduced efficacy following long-term treatment. In this study, we investigated the factors influencing the sensitivity of DS-8201 and developed effective combination regimens to optimize its therapeutic efficacy.
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