Krüppel-like factor 4 (KLF4) is an important transcription factor that is expressed in a variety of tissues and regulates many critical physiologic and cellular processes, including cell proliferation, differentiation, stem cell reprogramming, maintenance of genomic stability, and normal tissue homeostasis. KLF4 has both tumor suppressive and oncogenic functions in gastrointestinal and other cancers. These functions are thought to be context dependent, but how KLF4 exerts these differential functions and the molecular mechanisms behind them remain poorly understood. Recent studies have shown that the KLF4 gene undergoes alternative splicing, and the protein products of certain transcripts antagonize wild-type KLF4 function, suggesting an additional layer of regulation of KLF4 function. Therefore, detailed study of KLF4 alternative splicing may not only provide new insights into the complexity of KLF4 functions but also lead to rational targeting of KLF4 for cancer prevention and therapy.
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http://dx.doi.org/10.1016/j.canlet.2018.09.005 | DOI Listing |
Mol Biol Rep
January 2025
Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.
Background: Tubular injury triggered by hyperglycemia is an important pathological characteristic in diabetic nephropathy (DN). Accumulated advanced glycation end products and their precursor methylglyoxal (MGO), contribute to the development of DN. Carnosine has been shown to prevent the development of DN but the underlying mechanism still needs to be studied in depth.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pennsylvania, Philadelphia, PA, USA.
Background: Tau is a neuronal microtubule associated protein whose interactions with microtubules are regulated by phosphorylation. Tau has numerous putative phosphorylation sites, but it is unclear which combinations of Tau phosphorylation co-occur in the normal state and precisely how they impact Tau function. Adding further complexity, there are six major Tau isoforms arising from alternative splicing.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Barrow Neurological Institute, Phoenix, AZ, USA; Arizona State University, Tempe, AZ, USA.
Background: TDP-43 is an RNA binding protein that is a pathological hallmark of multiple neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The frequency of observed TDP-43 pathology is estimated at 97% in ALS, 45% in FTD and 40-57% in AD and is characterized by a mislocalization of TDP-43 from the nucleus to the cytoplasm. Indeed, TDP-43 is the third most common proteinopathy in AD, behind only Amyloid beta and Tau.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
TauC3 Biologics Limited, London, United Kingdom.
Background: Tau abnormalities are a central feature of Alzheimer's disease (AD) and the defining feature of non-AD tauopathies, which include frontotemporal lobar degeneration (FTLD) due to Pick's disease (PiD) or Mapt mutations (FTLD-tau), as well as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and others. Mapt transcripts undergo alternative splicing to produce 6 distinct isoforms. Exon 2 splicing produces 0, 1 or 2 inserts; exclusion or inclusion of exon 10 results in 3-repeat (3R) or 4-repeat (4R) forms, respectively.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Background: Alzheimer's disease (AD) hallmarks are amyloid plaques and tau tangles. APOE and TREM2 are the strongest genetic risk factors for AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized to play a central role in amyloid beta clearance and microglia activation in AD.
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