Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 Aug 1;373(Pt 3):713–722. doi: 10.1042/BJ20021902

p300/CBP-associated factor (P/CAF) interacts with nuclear respiratory factor-1 to regulate the UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-3 gene.

Hiroto Izumi 1, Ryo Ohta 1, Gunji Nagatani 1, Tomoko Ise 1, Yoshifumi Nakayama 1, Minoru Nomoto 1, Kimitoshi Kohno 1
PMCID: PMC1223531  PMID: 12720548

Abstract

We demonstrated recently that expression of the UDP- N -acetyl-alpha-D-galactosamine: polypeptide N -acetylgalactosaminyltrans-ferase-3 (GalNAc-T3) gene is restricted to epithelial glands [Nomoto, Izumi, Ise, Kato, Takano, Nagatani, Shibao, Ohta, Imamura, Kuwano, Matsuo, Yamada, Itoh and Kohno (1999) Cancer Res. 59, 6214-6222]. In the present study, we show that sodium butyrate treatment of human breast cancer MCF-7 cells transcriptionally activates the GalNAc-T3 gene. Transient transfection of plasmids containing a reporter gene under the control of GalNAc-T3 indicated that several transcriptional elements are involved in response to sodium butyrate, with the nuclear respiratory factor-1 (NRF-1)-binding motif located between -88 and -77nt being the most important. Incubation of a labelled probe encompassing the NRF-1-binding motif with a nuclear extract of sodium butyrate-treated MCF-7 cells yielded a higher level of specific DNA-protein complex versus controls. Flag-tagged NRF-1 expressed in MCF-7 cells can bind to the NRF-1-binding motif of the GalNAc-T3 promoter. Nuclear content of NRF-1 remained constant in MCF-7 cells treated with or without sodium butyrate. Moreover, NRF-1 interacts with and is acetylated by p300/CBP-associated factor (P/CAF). Acetylation of NRF-1 enhances DNA binding. Co-transfection of the GalNAc-T3 reporter plasmid with either NRF-1 or P/CAF expression plasmid resulted in the activation of the GalNAc-T3 promoter. These results indicate a correlation between acetylation of NRF-1 by P/CAF and the butyrate-induced expression of the GalNAc-T3 gene. Additionally, induced expression of P/CAF may be a component of the adenocarcinoma differentiation process.

Full Text

The Full Text of this article is available as a PDF (331.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett E. P., Hassan H., Hollingsworth M. A., Clausen H. A novel human UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase, GalNAc-T7, with specificity for partial GalNAc-glycosylated acceptor substrates. FEBS Lett. 1999 Oct 29;460(2):226–230. doi: 10.1016/s0014-5793(99)01268-5. [DOI] [PubMed] [Google Scholar]
  2. Bennett E. P., Hassan H., Mandel U., Hollingsworth M. A., Akisawa N., Ikematsu Y., Merkx G., van Kessel A. G., Olofsson S., Clausen H. Cloning and characterization of a close homologue of human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. J Biol Chem. 1999 Sep 3;274(36):25362–25370. doi: 10.1074/jbc.274.36.25362. [DOI] [PubMed] [Google Scholar]
  3. Bennett E. P., Hassan H., Mandel U., Mirgorodskaya E., Roepstorff P., Burchell J., Taylor-Papadimitriou J., Hollingsworth M. A., Merkx G., van Kessel A. G. Cloning of a human UDP-N-acetyl-alpha-D-Galactosamine:polypeptide N-acetylgalactosaminyltransferase that complements other GalNAc-transferases in complete O-glycosylation of the MUC1 tandem repeat. J Biol Chem. 1998 Nov 13;273(46):30472–30481. doi: 10.1074/jbc.273.46.30472. [DOI] [PubMed] [Google Scholar]
  4. Evans M. J., Scarpulla R. C. Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF, and intron Sp1 recognition sequences. J Biol Chem. 1989 Aug 25;264(24):14361–14368. [PubMed] [Google Scholar]
  5. Evans M. J., Scarpulla R. C. NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells. Genes Dev. 1990 Jun;4(6):1023–1034. doi: 10.1101/gad.4.6.1023. [DOI] [PubMed] [Google Scholar]
  6. Frommel T. O., Coon J. S., Tsuruo T., Roninson I. B. Variable effects of sodium butyrate on the expression and function of the MDR1 (P-glycoprotein) gene in colon carcinoma cell lines. Int J Cancer. 1993 Sep 9;55(2):297–302. doi: 10.1002/ijc.2910550221. [DOI] [PubMed] [Google Scholar]
  7. Gillenwater A., Zou C. P., Zhong M., Lotan R. Effects of sodium butyrate on growth, differentiation, and apoptosis in head and neck squamous carcinoma cell lines. Head Neck. 2000 May;22(3):247–256. doi: 10.1002/(sici)1097-0347(200005)22:3<247::aid-hed7>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  8. Gopalakrishnan L., Scarpulla R. C. Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1. J Biol Chem. 1995 Jul 28;270(30):18019–18025. doi: 10.1074/jbc.270.30.18019. [DOI] [PubMed] [Google Scholar]
  9. Gugneja S., Scarpulla R. C. Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding. J Biol Chem. 1997 Jul 25;272(30):18732–18739. doi: 10.1074/jbc.272.30.18732. [DOI] [PubMed] [Google Scholar]
  10. Hagen F. K., Ten Hagen K. G., Beres T. M., Balys M. M., VanWuyckhuyse B. C., Tabak L. A. cDNA cloning and expression of a novel UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. J Biol Chem. 1997 May 23;272(21):13843–13848. doi: 10.1074/jbc.272.21.13843. [DOI] [PubMed] [Google Scholar]
  11. Hagen F. K., Van Wuyckhuyse B., Tabak L. A. Purification, cloning, and expression of a bovine UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferase. J Biol Chem. 1993 Sep 5;268(25):18960–18965. [PubMed] [Google Scholar]
  12. Homa F. L., Hollander T., Lehman D. J., Thomsen D. R., Elhammer A. P. Isolation and expression of a cDNA clone encoding a bovine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. J Biol Chem. 1993 Jun 15;268(17):12609–12616. [PubMed] [Google Scholar]
  13. Huang H., Reed C. P., Zhang J. S., Shridhar V., Wang L., Smith D. I. Carboxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells. Cancer Res. 1999 Jun 15;59(12):2981–2988. [PubMed] [Google Scholar]
  14. Izumi H., Molander C., Penn L. Z., Ishisaki A., Kohno K., Funa K. Mechanism for the transcriptional repression by c-Myc on PDGF beta-receptor. J Cell Sci. 2001 Apr;114(Pt 8):1533–1544. doi: 10.1242/jcs.114.8.1533. [DOI] [PubMed] [Google Scholar]
  15. Litvak D. A., Hwang K. O., Evers B. M., Townsend C. M., Jr Induction of apoptosis in human gastric cancer by sodium butyrate. Anticancer Res. 2000 Mar-Apr;20(2A):779–784. [PubMed] [Google Scholar]
  16. Liu L., Scolnick D. M., Trievel R. C., Zhang H. B., Marmorstein R., Halazonetis T. D., Berger S. L. p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol. 1999 Feb;19(2):1202–1209. doi: 10.1128/mcb.19.2.1202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liu X., Kim C. N., Yang J., Jemmerson R., Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996 Jul 12;86(1):147–157. doi: 10.1016/s0092-8674(00)80085-9. [DOI] [PubMed] [Google Scholar]
  18. Miranda S., Foncea R., Guerrero J., Leighton F. Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells. Biochem Biophys Res Commun. 1999 Apr 29;258(1):44–49. doi: 10.1006/bbrc.1999.0580. [DOI] [PubMed] [Google Scholar]
  19. Moriuchi M., Moriuchi H., Turner W., Fauci A. S. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. J Immunol. 1997 Nov 1;159(9):4322–4329. [PubMed] [Google Scholar]
  20. Murakami T., Shibuya I., Ise T., Chen Z. S., Akiyama S., Nakagawa M., Izumi H., Nakamura T., Matsuo K., Yamada Y. Elevated expression of vacuolar proton pump genes and cellular PH in cisplatin resistance. Int J Cancer. 2001 Sep;93(6):869–874. doi: 10.1002/ijc.1418. [DOI] [PubMed] [Google Scholar]
  21. Niv Y., Byrd J. C., Ho S. B., Dahiya R., Kim Y. S. Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro. Int J Cancer. 1992 Jan 2;50(1):147–152. doi: 10.1002/ijc.2910500129. [DOI] [PubMed] [Google Scholar]
  22. Nomoto M., Izumi H., Ise T., Kato K., Takano H., Nagatani G., Shibao K., Ohta R., Imamura T., Kuwano M. Structural basis for the regulation of UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 gene expression in adenocarcinoma cells. Cancer Res. 1999 Dec 15;59(24):6214–6222. [PubMed] [Google Scholar]
  23. Novotny V., Prieschl E. E., Csonga R., Fabjani G., Baumruker T. Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells. Nucleic Acids Res. 1998 Dec 1;26(23):5480–5485. doi: 10.1093/nar/26.23.5480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rivero J. A., Adunyah S. E. Sodium butyrate stimulates PKC activation and induces differential expression of certain PKC isoforms during erythroid differentiation. Biochem Biophys Res Commun. 1998 Jul 30;248(3):664–668. doi: 10.1006/bbrc.1998.9041. [DOI] [PubMed] [Google Scholar]
  26. Shibao Kazunori, Izumi Hiroto, Nakayama Yoshifumi, Ohta Ryo, Nagata Naoki, Nomoto Minoru, Matsuo Ken-ichi, Yamada Yuji, Kitazato Kenji, Itoh Hideaki. Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide galNAc N-acetylgalactosaminyl transferase-3 in relation to differentiation and prognosis in patients with colorectal carcinoma. Cancer. 2002 Apr 1;94(7):1939–1946. doi: 10.1002/cncr.10423. [DOI] [PubMed] [Google Scholar]
  27. Solecki D., Bernhardt G., Lipp M., Wimmer E. Identification of a nuclear respiratory factor-1 binding site within the core promoter of the human polio virus receptor/CD155 gene. J Biol Chem. 2000 Apr 28;275(17):12453–12462. doi: 10.1074/jbc.275.17.12453. [DOI] [PubMed] [Google Scholar]
  28. Sutherlin M. E., Nishimori I., Caffrey T., Bennett E. P., Hassan H., Mandel U., Mack D., Iwamura T., Clausen H., Hollingsworth M. A. Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines. Cancer Res. 1997 Nov 1;57(21):4744–4748. [PubMed] [Google Scholar]
  29. Ten Hagen K. G., Hagen F. K., Balys M. M., Beres T. M., Van Wuyckhuyse B., Tabak L. A. Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem. 1998 Oct 16;273(42):27749–27754. doi: 10.1074/jbc.273.42.27749. [DOI] [PubMed] [Google Scholar]
  30. Ten Hagen K. G., Tetaert D., Hagen F. K., Richet C., Beres T. M., Gagnon J., Balys M. M., VanWuyckhuyse B., Bedi G. S., Degand P. Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity. J Biol Chem. 1999 Sep 24;274(39):27867–27874. doi: 10.1074/jbc.274.39.27867. [DOI] [PubMed] [Google Scholar]
  31. Uramoto Hidetaka, Izumi Hiroto, Ise Tomoko, Tada Mitsuhiro, Uchiumi Takeshi, Kuwano Michihiko, Yasumoto Kosei, Funa Keiko, Kohno Kimitoshi. p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression. J Biol Chem. 2002 Jun 21;277(35):31694–31702. doi: 10.1074/jbc.M200266200. [DOI] [PubMed] [Google Scholar]
  32. Wandall H. H., Hassan H., Mirgorodskaya E., Kristensen A. K., Roepstorff P., Bennett E. P., Nielsen P. A., Hollingsworth M. A., Burchell J., Taylor-Papadimitriou J. Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem. 1997 Sep 19;272(38):23503–23514. doi: 10.1074/jbc.272.38.23503. [DOI] [PubMed] [Google Scholar]
  33. White T., Bennett E. P., Takio K., Sørensen T., Bonding N., Clausen H. Purification and cDNA cloning of a human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. J Biol Chem. 1995 Oct 13;270(41):24156–24165. doi: 10.1074/jbc.270.41.24156. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES