17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Acetyltransferases and tumour suppression

      research-article
      1 , 1
      Breast Cancer Research
      BioMed Central
      acetylation, acetyltransferases, CBP, E1A, p300, tumour suppressors

      Read this article at

      ScienceOpenPublisherPMC
      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

          The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers.

          Related collections

          Most cited references22

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

          Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.

          The tumor suppressor p53 exerts antiproliferation effects through its ability to function as a sequence-specific DNA-binding transcription factor. Here, we demonstrate that p53 can be modified by acetylation both in vivo and in vitro. Remarkably, the site of p53 that is acetylated by its coactivator, p300, resides in a C-terminal domain known to be critical for the regulation of p53 DNA binding. Furthermore, the acetylation of p53 can dramatically stimulate its sequence-specific DNA-binding activity, possibly as a result of an acetylation-induced conformational change. These observations clearly indicate a novel pathway for p53 activation and, importantly, provide an example of an acetylation-mediated change in the function of a nonhistone regulatory protein. These results have significant implications regarding the molecular mechanisms of various acetyltransferase-containing transcriptional coactivators whose primary targets have been presumed to be histones.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The CBP co-activator is a histone acetyltransferase.

            The CBP protein acts as a transcriptional adaptor for many different transcription factors by directly contacting DNA-bound activators. One mechanism by which CBP is thought to stimulate transcription is by recruiting the histone acetyltransferase (HAT) P/CAF to the promoter. Here we show that CBP has intrinsic HAT activity. The HAT domain of CBP is adjacent to the binding site for the transcriptional activator E1A. Although E1A displaces P/CAF from CBP, it does not disrupt the CBP-associated HAT activity. Thus E1A carries HAT activity when complexed with CBP. Targeting CBP-associated HAT activity to specific promoters may therefore be a mechanism by which E1A acts as a transcriptional activator.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Acetylation: a regulatory modification to rival phosphorylation?

              The fact that histones are modified by acetylation has been known for almost 30 years. The recent identification of enzymes that regulate histone acetylation has revealed a broader use of this modification than was suspected previously. Acetylases are now known to modify a variety of proteins, including transcription factors, nuclear import factors and alpha-tubulin. Acetylation regulates many diverse functions, including DNA recognition, protein-protein interaction and protein stability. There is even a conserved structure, the bromodomain, that recognizes acetylated residues and may serve as a signalling domain. If you think all this sounds familiar, it should be. These are features characteristic of kinases. So, is acetylation a modification analogous to phosphorylation? This review sets out what we know about the broader substrate specificity and regulation of acetyl- ases and goes on to compare acetylation with the process of phosphorylation.
                Bookmark

                Author and article information

                Journal
                Breast Cancer Res
                Breast Cancer Research
                BioMed Central (London )
                1465-5411
                1465-542X
                2000
                24 May 2000
                : 2
                : 4
                : 244-246
                Affiliations
                [1 ]NCI-FCRDC, Frederick, Maryland, USA.
                Article
                bcr63
                10.1186/bcr63
                138782
                11250715
                ff55b286-f3aa-4382-a801-2cc29d0578c3
                Copyright © 2000 Current Science Ltd
                History
                : 17 April 2000
                : 27 April 2000
                : 2 May 2000
                : 2 May 2000
                Categories
                Commentary

                Oncology & Radiotherapy
                acetyltransferases,e1a,cbp,acetylation,tumour suppressors,p300
                Oncology & Radiotherapy
                acetyltransferases, e1a, cbp, acetylation, tumour suppressors, p300

                Comments

                Comment on this article