20
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Role of Caspase-2 in Regulating Cell Fate

      review-article
      , *
      Cells
      MDPI
      caspase-2, procaspase, apoptosis, splice variants, activation, intrinsic, extrinsic, neurons

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Caspase-2 is the most evolutionarily conserved member of the mammalian caspase family and has been implicated in both apoptotic and non-apoptotic signaling pathways, including tumor suppression, cell cycle regulation, and DNA repair. A myriad of signaling molecules is associated with the tight regulation of caspase-2 to mediate multiple cellular processes far beyond apoptotic cell death. This review provides a comprehensive overview of the literature pertaining to possible sophisticated molecular mechanisms underlying the multifaceted process of caspase-2 activation and to highlight its interplay between factors that promote or suppress apoptosis in a complicated regulatory network that determines the fate of a cell from its birth and throughout its life.

          Related collections

          Most cited references297

          • Record: found
          • Abstract: found
          • Article: not found

          Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.

          Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Requirement for p53 and p21 to sustain G2 arrest after DNA damage.

            After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma radiated cells progressed into mitosis and exhibited a G2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2.

              DNA-damaging agents signal to p53 through as yet unidentified posttranscriptional mechanisms. Here we show that phosphorylation of human p53 at serine 15 occurs after DNA damage and that this leads to reduced interaction of p53 with its negative regulator, the oncoprotein MDM2, in vivo and in vitro. Furthermore, using purified DNA-dependent protein kinase (DNA-PK), we demonstrate that phosphorylation of p53 at serines 15 and 37 impairs the ability of MDM2 to inhibit p53-dependent transactivation. We present evidence that these effects are most likely due to a conformational change induced upon phosphorylation of p53. Our studies provide a plausible mechanism by which the induction of p53 can be modulated by DNA-PK (or other protein kinases with similar specificity) in response to DNA damage.
                Bookmark

                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                19 May 2020
                May 2020
                : 9
                : 5
                : 1259
                Affiliations
                Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; v.vigneswara@ 123456bham.ac.uk
                Author notes
                [* ]Correspondence: z.ahmed.1@ 123456bham.ac.uk
                Author information
                https://orcid.org/0000-0001-6267-6442
                Article
                cells-09-01259
                10.3390/cells9051259
                7290664
                32438737
                249bed27-6d0d-4ad7-add1-ea89a1ec771b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 April 2020
                : 12 May 2020
                Categories
                Review

                caspase-2,procaspase,apoptosis,splice variants,activation,intrinsic,extrinsic,neurons

                Comments

                Comment on this article