Key points are not available for this paper at this time.
Sp1 is a ubiquitously expressed transcription factor that binds GC-rich cis elements. Many posttranslational modifications have been implicated in the regulation of Sp1 activity. We now provide evidence for a novel mechanism of Sp1 regulation involving the small ubiquitin-like modifier (SUMO-1). Western blot analysis revealed a high molecular mass Sp1 of 125 kDa that is stabilized by a selective SUMO hydrolase inhibitor and destabilized by a specific SUMO-1 hydrolase. The covalent modification of Sp1 by endogenous SUMO-1 and SUMO-1 that has been fused to green fluorescent protein was demonstrated using transient transfection assays. A high probability sumoylation consensus motif, VK16IE18, is located within the N-terminal negative regulatory domain of Sp1. Either arginine substitution for lysine 16 (Sp1(K16R)) or alanine substitution for glutamic acid 18 (Sp1(E18A)), abrogated Sp1 sumoylation. In vitro SUMO-1 covalently bound affinity-purified GST-Sp1, but not GST-Sp1(K16R). In vivo Sp1 was determined to be N-terminally cleaved, while Sp1(K16R) could not be cleaved indicating that sumoylation and cleavage are coupled through the key regulatory lysine 16. This coupling was evident by the demonstration of an inverse relationship between cellular SUMO-modified Sp1 and N-terminally cleaved Sp1. Compared with Sp1, sumoylation-deficient Sp1(E18A) exhibited enhanced cleavage and was a better transcriptional activator, while constitutively SUMO-1-modified Sp1 was deficient in proteolytic processing and repressed Sp1 transcriptional activity. The repressive effect of sumoylation on Sp1 activity is emphasized through the use of a GAL4 based transactivation assay. A model is proposed defining a mechanism by which sumoylation preserves the integrity of a negative regulatory domain thereby allowing for the inhibition of Sp-dependent transcription. Sp1 is a ubiquitously expressed transcription factor that binds GC-rich cis elements. Many posttranslational modifications have been implicated in the regulation of Sp1 activity. We now provide evidence for a novel mechanism of Sp1 regulation involving the small ubiquitin-like modifier (SUMO-1). Western blot analysis revealed a high molecular mass Sp1 of 125 kDa that is stabilized by a selective SUMO hydrolase inhibitor and destabilized by a specific SUMO-1 hydrolase. The covalent modification of Sp1 by endogenous SUMO-1 and SUMO-1 that has been fused to green fluorescent protein was demonstrated using transient transfection assays. A high probability sumoylation consensus motif, VK16IE18, is located within the N-terminal negative regulatory domain of Sp1. Either arginine substitution for lysine 16 (Sp1(K16R)) or alanine substitution for glutamic acid 18 (Sp1(E18A)), abrogated Sp1 sumoylation. In vitro SUMO-1 covalently bound affinity-purified GST-Sp1, but not GST-Sp1(K16R). In vivo Sp1 was determined to be N-terminally cleaved, while Sp1(K16R) could not be cleaved indicating that sumoylation and cleavage are coupled through the key regulatory lysine 16. This coupling was evident by the demonstration of an inverse relationship between cellular SUMO-modified Sp1 and N-terminally cleaved Sp1. Compared with Sp1, sumoylation-deficient Sp1(E18A) exhibited enhanced cleavage and was a better transcriptional activator, while constitutively SUMO-1-modified Sp1 was deficient in proteolytic processing and repressed Sp1 transcriptional activity. The repressive effect of sumoylation on Sp1 activity is emphasized through the use of a GAL4 based transactivation assay. A model is proposed defining a mechanism by which sumoylation preserves the integrity of a negative regulatory domain thereby allowing for the inhibition of Sp-dependent transcription. Sp1 was one of the first mammalian transcription factors to be cloned and biochemically characterized (1Briggs M.R. Kadonaga J.T. Bell S.P. Tjian R. Science. 1986; 234: 47-52Crossref PubMed Scopus (1058) Google Scholar, 2Kadonaga J.T. Carner K.R. Masiarz F.R. Tjian R. Cell. 1987; 51: 1079-1090Abstract Full Text PDF PubMed Scopus (1252) Google Scholar). Sp1 is representative of a large Sp/KLF family (greater than 20 members) characterized by their affinity for GC-rich cis elements found in the promoters of many housekeeping genes as well as inducible genes (3Black A.R. Black J.D. Azizkhan-Clifford J. J. Cell. Physiol. 2001; 188: 143-160Crossref PubMed Scopus (898) Google Scholar, 4Suske G. Gene (Amst.). 1999; 238: 291-300Crossref PubMed Scopus (985) Google Scholar). Thus, Sp1 is involved in virtually all facets of cellular function. Of particular interest is Sp1 regulation of G1 phase TATA-less promoters, which govern cell growth, cell cycle regulation, differentiation, and apoptosis (5Pugh B.F. Tjian R. Genes Dev. 1991; 5: 1935-1945Crossref PubMed Scopus (477) Google Scholar, 6Zenzie-Gregory B. Khachi A. Garraway I.P. Smale S.T. Mol. Cell. Biol. 1993; 13: 3841-3892Crossref PubMed Scopus (91) Google Scholar). The Sp1 molecule is organized into strong glutamine-rich activating domains (A (residues 83–262) and B (residues 263–542)) and weak activating domains (C (residues 543–610) and D (residues 709–778)). A highly conserved zinc finger region (residues 615–708) responsible for DNA binding is located between domains C and D (7Courey A.J. Tjian R. Cell. 1988; 55: 887-898Abstract Full Text PDF PubMed Scopus (1079) Google Scholar). The N terminus (amino acids 1–82) endows Sp1 with repressor activity (8Murata Y. Kim H.G. Rogers K.T. Udvadia A.J. Horowitz J.M. J. Biol. Chem. 1994; 269: 20674-20681Abstract Full Text PDF PubMed Google Scholar, 9Lee J.A. Suh D.C. Kang J.E. Kim M.H. Park H. Lee M.N. Kim J.M. Jeon B.N. Roh H.E. Yu M.Y. Choi K.Y. Kim K.Y. Hur M.W. J. Biol. Chem. 2005; 280: 28061-28071Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar). A stretch of conserved amino acids known as the Sp box is located at the N terminus of Sp1–8. This element contains an endoproteolytic cleavage site situated close to a region that targets Sp1 proteasome-dependent degradation in vitro (10Su K. Roos M.D. Yang X. Han I. Paterson A.J. Kudlow J.E. J. Biol. Chem. 1999; 274: 15194-15202Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar). The complexity of Sp1 gene regulation and function is explained in part through postranslational modifications, which include phosphorylation, glycosylation, ubiquitinylation, acetylation, and ribosylation (11Bouwman P. Philipsen S. Mol. Cell. Endocrinol. 2002; 195: 27-38Crossref PubMed Scopus (401) Google Scholar). For example, phosphorylation by cAMP-dependent protein kinase enhances Sp1 DNA binding and thereby increases its transcriptional activity (12Rohlff C. Ahmad S. Borellini F. Lei J. Glazer R.I. J. Biol. Chem. 1997; 272: 21137-21141Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar). Sp1 phosphorylation also increases ubiquitinylation and subsequent proteolysis and thereby decreases Sp1 nuclear levels (13Leggett R.W. Armstrong S.A. Barry D. Mueller C.R. J. Biol. Chem. 1995; 270: 25879-25884Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 14Mortensen E.R. Marks P.A. Shiotani A. Merchant J.L. J. Biol. Chem. 1997; 272: 16540-16547Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar). O-Linked N-acetylglucosamine (O-GlcNAc) protects Sp1 from proteolysis, and since many of the same serines and threonines may be used for phosphorylation or glycosylation, there is an inverse relationship between Sp1 phosphorylation and glycosylation (15Han I. Kudlow J.E. Mol. Cell. Biol. 1997; 17: 2550-2558Crossref PubMed Scopus (377) Google Scholar, 16Wells L. Vosseller K. Hart G.W. Science. 2001; 291: 2376-2378Crossref PubMed Scopus (805) Google Scholar). Glycosylation has been reported to enhance Sp-dependent transcription in some contexts, while in others, glycosylation interferes with Sp1/TAF factor binding resulting in transcriptional repression (17Du X.L. Edelstein D. Rossetti L. Fantus I.G. Goldberg H. Ziyadeh F. Wu J. Brownlee M. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 12222-12226Crossref PubMed Scopus (896) Google Scholar, 18Yang X. Su K. Roos M.D. Chang Q. Paterson A.J. Kudlow J.E. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 6611-6616Crossref PubMed Scopus (235) Google Scholar). Acetylation activates Sp1 transcriptional potential by enhancing Sp1 DNA binding (19Huang W. Zhao S. Ammanamanchi S. Brattain M. Venkatasubbarao K. Freeman J.W. J. Biol. Chem. 2005; 280: 10047-10054Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar). Lysines are particularly interesting sites of protein modification because of the large number of different interactions they undergo including acetylation, ubiquitinylation, methylation, or modification by various ubiquitin-like modifiers including the small ubiquitin-like modifier (SUMO) 2The abbreviations used are: SUMO, small ubiquitin-like modifier; NRD, negative regulatory domain; NEM, N-ethylmaleimide; SL2, Schneider line-2; GFP, green fluorescent protein; GST, glutathione S-transferase; LLnL, N-acetyl-l-leucinyl-l-norleucinal; HA, hemagglutinin; DHFR, dihydrofolate reductase; DBD, DNA binding domain. (20Freiman R.N. Tjian R. Cell. 2003; 112: 11-17Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Sumoylation is the process whereby SUMO-1, -2, or -3 is covalently and reversibly bound to specific lysines of target proteins using homologous ubiquitin-like enzymes (E1, E2, and E3). SUMO-1 is a 101-amino acid peptide sharing 18% identity to ubiquitin; not as a for protein sumoylation interactions resulting in modification of A. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar). Sumoylation has been implicated in regulatory including protein regulation, transcription factor DNA and protein The of SUMO-1 many transcription factors a for sumoylation in the regulation of gene Sumoylation transcriptional activity some that sumoylation enhances factor activity G. Dev. 2003; 13: PubMed Scopus Google Scholar, A. J. M. 2003; PubMed Scopus Google Scholar). evidence for the SUMO-1 modification of Sp1 and 16 as the We also that lysine 16 Sp1 N-terminal cleavage in the Sp1 N terminus is a binding that SUMO-1 modification at lysine 16 Sp1 proteolytic a sumoylation-deficient Sp1, and a constitutively SUMO-1-modified Sp1. The that Sp1(E18A) is a better for N-terminal cleavage and a better of transcription with Sp1. In the constitutively Sp1 is not a for N-terminal cleavage and is a transcription evidence that sumoylation Sp1 activity is through the use of a assay. a novel mechanism whereby sumoylation Sp1 activity by the integrity of a negative regulatory domain. A model is proposed posttranslational at lysine 16 in the of Sp-dependent transcription. from the in with in a at from and in with Schneider at in cell with and and from was from was from was through and was a from Black A.R. D. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). a substitution at lysine 16 for arginine using a with the and its Sp1 in which glutamic acid 18 was with alanine was with the has been Brattain Horowitz J.M. Cell. 2005; 17: PubMed Scopus Google Scholar). and from was with to the Sp1 gene and with a Sp1 gene in a using the and A mammalian that the of a was from F. A. G. H. A. M. F. G. J. 2002; PubMed Scopus Google Scholar). was by L. S. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). and from J. Horowitz (8Murata Y. Kim H.G. Rogers K.T. Udvadia A.J. Horowitz J.M. J. Biol. Chem. 1994; 269: 20674-20681Abstract Full Text PDF PubMed Google Scholar). A constitutively SUMO-modified Sp1 was using a SUMO-1 in a including the and to a SUMO-1 amino acids was to Sp1 with and the SUMO-1 was with to Sp1 a and and with using as the was used to for and 18 was used to DNA The and for the of protein in cell was used to activity. was in a are representative of at Western cell by in and proteins on For in with in the of inhibitor and by at at for with and protein for at The by and to in on and to using a with in with 20 and with for at with to using a to the and through In in vitro sumoylation was from and expressed GST, GST-Sp1, and using as and used as in the in vitro was used as a and and Western to Sp1 a by a of SUMO and by a SUMO a the Sp1 family was determined to be and and Sp1 to with the Brattain Horowitz J.M. Cell. 2005; 17: PubMed Scopus Google Scholar). This to Sp1 be SUMO-1 cell with bound to or with protein bound to Western blot the Sp1 protein at kDa as well as high molecular mass proteins proteins in a molecular mass by 20 kDa or the SUMO-modified a small of the The Western a but with complexity that Sp1 may with many proteins not This that endogenous Sp1 and to specific to a Sp1 in the In the with a Sp1 and in to SUMO-1 The resulting Western blot revealed Sp1 at and kDa of the same a novel of 125 kDa was not proteins indicating that the proteins are B and proteins are but be stabilized in the of a selective inhibitor of enzymes K. Black A.R. Azizkhan-Clifford J. J. 2002; PubMed Scopus Google Scholar, A. H. M. M. K. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). the novel protein is SUMO-modified Sp1, be to be in and stabilized in with and or in the of was the novel Sp1 that the high molecular mass Sp1 is a SUMO-modified with a Sp1 or with a a specific SUMO hydrolase. In the of the Sp1 was abrogated evidence that Sp1 is Sp1 SUMO-1 in Sp1 is SUMO-1 in a Sp1 or with a SUMO-1 fused to green fluorescent protein Sp1 a novel high molecular mass Sp1 protein resulting from the covalent between Sp1 and be cell and by with of Sp1 and to the of a novel high molecular mass Sp1 protein In the endogenous SUMO bound to Sp1, which is in This from for the between the levels of endogenous Sp1 and the expressed SUMO The high molecular mass protein was not in with that the high molecular mass protein is by the from with an and the resulting was with and with B and The novel high molecular mass Sp1 with evidence for the specific of SUMO-1 to Sp1. 16 for Sp1 high probability sumoylation consensus was within the Sp1 N lysine 16 was with an or Sp1 exhibited the Sp1 not A and that lysine 16 is for Sp1 sumoylation. In Sumoylation of that Sp1 is SUMO-1 and that lysine 16 is responsible for an in vitro sumoylation assay. The sumoylation and and the of GST, GST-Sp1, and from used as in assay. was not SUMO-1-modified not Western blot revealed that was not exhibited one SUMO-1-modified The of sumoylation 16 for Sp1 N-terminal in that sumoylation at the N terminus of sumoylation may be involved in an N-terminal process Sp1 transcription. in vitro has demonstrated that a activator, Sp1 protein cleavage at amino acid and in with the was (10Su K. Roos M.D. Yang X. Han I. Paterson A.J. Kudlow J.E. J. Biol. Chem. 1999; 274: 15194-15202Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar). We that sumoylation proteolytic cleavage and thereby the integrity of Sp1 binding domain. was first to that Sp1 could be N-terminally cleaved in vivo to been in The Sp1 proteins used in an N-terminal and allowing for Western blot of a cleavage been used in vitro to and used to Sp proteins and with B and and or with and Western blot that of an Sp1 cleavage as by the cleavage is abrogated by with a as in that the was through N-terminal cleavage was by its of in vivo the in vitro demonstration that Sp1 proteolytic of the Sp1(K16R) protein molecular mass proteins of and kDa and and The molecular mass of Sp1 is and that the molecular mass Sp1(K16R) is by as well as and be a cleavage that the molecular mass the Sp1 is not by a inhibitor or We that Sp1(K16R) is not N-terminally cleaved and that its may be to that Sp1 in vivo proteolytic processing and that Sp1 sumoylation and N-terminal cleavage are coupled through lysine 16. the of Sumoylation and that the Sp1(K16R) not be for the of sumoylation on Sp-dependent since not be to between the by N-terminal We that the conserved glutamic within the sumoylation motif, a Sp1 with an lysine 16. The Sp1 sumoylation with its conserved glutamic acid is in in to the glutamic acid 18 is lysine This lysine is not to be for Sp1 has been that lysines in the of a sumoylation may sumoylation. glutamic acid 18 was with alanine (Sp1(E18A)), and lysine was with arginine enhance of Sp1 with the Sp proteins and Western that Sp1 and and for while Sp1(K16R) and Sp1(E18A) not and We determined the sumoylation-deficient Sp1(E18A) the potential to be N-terminally as and with or and by Western blot in Sp1(E18A) is a for the process of N-terminal The of sumoylation and cleavage are in the Sp1(E18A) thereby allowing to the of sumoylation on Sp1 function. Sumoylation N sumoylation and N-terminal cleavage are coupled through Sp1 lysine an inverse relationship between the cellular of and cleaved Sp1. Sp1 was with of SUMO-1 in with Western blot that the Sp1 decreases with the in SUMO-modified Sp1 that are A and to the effect of sumoylation on Sp1 activity is because a small of Sp1 is a analysis of Sp1 a constitutively SUMO-modified Sp1. a the SUMO-1 gene the amino which include the SUMO hydrolase cleavage was fused to the of the Sp1 sumoylation the cleavage of Sp1, Sp1, and constitutively SUMO-modified Sp1 with by Western blot analysis SUMO-modified Sp1 could not be cleaved, as by the of an In with Sp1 was a better for N-terminal cleavage with Sp1 thereby that sumoylation Sp1 Sumoylation The N terminus of Sp1 is a binding and sumoylation the integrity of SUMO-modified Sp1 Sp-dependent transcription. The of was to the effect of sumoylation on Sp1 transcriptional activity. sumoylation endogenous Sp1 with a Sp1 binding of a was in there is a relationship between the of expressed and the in Sp-dependent transcription. that sumoylation endogenous with the and the Sp endogenous Sp1 resulting in a high and Sp1 a The high to between the of Sp1 and as in Sp1 is with SUMO-modified Sp1, and the endogenous Sp1 activity was from the activity by Sp The that repressed Sp1 transcriptional activity by and the Western that the Sp protein levels with a and the Sp was that protein levels in the cell and could not be used in as by the Western blot in Sp1 and Sp1(E18A) found in a from with Sp1 activity in is than the and Sp1(E18A) than Sp1 a small of Sp1 is the transcriptional between Sp1 and Sp1(E18A) that sumoylation an in the of transcription. In the with the Compared with the used activity and activity is than that of and that the Sp1 N terminus is a negative regulatory domain and the SUMO-1 modifier as a in that lysine 16 is a key regulatory Sp1 and ubiquitinylation at lysine 16 the is the N-terminal cleavage of a binding domain and thereby a Sp1 SUMO-1 for the covalent binding of lysine the integrity is allowing the of and subsequent repression of Sp-dependent transcription. from the cell that posttranslational modifications the activity of factors resulting in in gene transcriptional activator, Sp1, is by including phosphorylation, glycosylation, acetylation, ubiquitinylation, as sumoylation. has been reported that Sp1, is not a for SUMO-1 modification A. G. H. A. M. F. G. J. 2002; PubMed Scopus Google the Sp1 used to the N terminus and not the key sumoylation site in molecular and evidence for Sp1 sumoylation. Sp1 with an Brattain Horowitz J.M. Cell. 2005; 17: PubMed Scopus Google Scholar). protein is stabilized in the of a selective SUMO-1 hydrolase inhibitor and abrogated in the of a specific SUMO hydrolase. Western blot analysis from cell Sp1 and that SUMO-1 covalently binds to Sp1. Sp1 a sumoylation consensus motif, which is located within an N-terminal negative regulatory domain. of arginine for the lysine abrogated Sp1 sumoylation. A sumoylation was used to that was SUMO-1 was revealed in of Sp1(K16R) with Sp1 in binding using an Sp1 negative are not in but the are to reported in an of sumoylation Brattain Horowitz J.M. Cell. 2005; 17: PubMed Scopus Google Scholar). The N terminus of Sp1 endoproteolytic cleavage in vitro resulting in an (10Su K. Roos M.D. Yang X. Han I. Paterson A.J. Kudlow J.E. J. Biol. Chem. 1999; 274: 15194-15202Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar). The N terminus of Sp1 is a negative regulatory which binds J.A. Suh D.C. Kang J.E. Kim M.H. Park H. Lee M.N. Kim J.M. Jeon B.N. Roh H.E. Yu M.Y. Choi K.Y. Kim K.Y. Hur M.W. J. Biol. Chem. 2005; 280: 28061-28071Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar). sumoylation has been implicated in and in the of that sumoylation may one or of Sp1 N-terminal in vitro by Kudlow and (10Su K. Roos M.D. Yang X. Han I. Paterson A.J. Kudlow J.E. J. Biol. Chem. 1999; 274: 15194-15202Abstract Full Text Full Text PDF PubMed Scopus (96) Google demonstrated that the first amino acids of Sp1 is a site for proteasome-dependent N-terminal The activator, was used to Sp1 cleavage into an In with the in vitro in vivo demonstrated that the of an in a proteasome-dependent that Sp1(K16R) could not be N-terminally cleaved in that from lysine 16 is also for proteasome-dependent The molecular mass of Sp1(K16R) are to be Sp1 that are stabilized by the of the lysine 16. an lysine was for sumoylation N-terminal in its there is a in Sp1 cleavage Many on proteins a of the lysine may for of which may be responsible for the determined that Sp1 lysine 16 is a key molecular the of sumoylation and N-terminal was to a sumoylation-deficient Sp1 that was to proteolytic This was through of the conserved glutamic acid 18 found in the Sp1 which in a sumoylation deficient cleavage Sp protein The SUMO-modified of a protein a small of the and SUMO binds in transient thereby to the of In an to a constitutively SUMO-modified Sp1 by the SUMO-1 its cleavage to the of the Sp1 have been used involving covalent of to the domain and SUMO-1 to a protein to Science. 2001; PubMed Scopus Google Scholar). with a constitutively SUMO-modified Sp1 and Sp1 (Sp1(E18A)), a could not cleavage of a constitutively SUMO-modified Sp1(E18A) enhanced N-terminal cleavage with Sp1 evidence that sumoylation Sp1 cleavage is by a demonstration the inverse relationship between cellular of SUMO-modified Sp1 and cleaved Sp1 C and This Western blot also that is Sp1 that may undergo proteolytic is that phosphorylation ubiquitinylation in proteasome-dependent Sp1 proteolytic processing is to that in of the of sumoylation in Sp-dependent a with of the sumoylation a negative regulatory effect on Sp-dependent transcription. there may be to In the the and Sp proteins in have endogenous Sp1 in the which in high that the activity of Sp1. This may Sp1 a activity. The are with endogenous activity to Sp1 activity. The that constitutively SUMO-modified Sp1 was a with Sp1. between Sp1 and Sp1(E18A) not The SL2, is of endogenous Sp1 and is the cell for small in Sp1 activity. The Sp1 and Sp1(E18A) found in protein levels in SL2, while protein levels found in and could not be in assay. In Sp1 exhibited activity activity and Sp1(E18A) genes than Sp1 and in activity have been between SUMO-1-modified and of transcription factors including and Brattain Horowitz J.M. Cell. 2005; 17: PubMed Scopus Google Scholar, S. M. F. Y. A. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, H. U. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: PubMed Scopus Google Scholar). that a small of Sp1 is in activity that sumoylation an in Sp-dependent transcription. between and sumoylation-deficient Sp1, with the binding site is the first a has been with Sp1 Sp1 The between N-terminally Sp1 and Sp1 that of of Sp1 as a transcriptional may to be since analysis of Sp1 has been using the repressor function of the Sp1 N terminus and demonstrated that Sp1 sumoylation a in in vitro that an Sp1 was highly high and levels and an in the degradation of Sp1. proteins are with their a between protein and We a model in whereby the cleavage is a transcription factor the negative of SUMO-1 is as a modifier of is a of transcription indicating the of sumoylation in gene The of SUMO-1 has been reported to transactivation through transcription factor DNA that posttranslational modifications, proposed in sumoylation may also proteolytic is that sumoylation at elements H. U. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: PubMed Scopus Google and that sumoylation the of to the For example, and a negative regulatory effect through the of the D. D. A. Mol. Cell. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, Y. R.N. Proc. Natl. Acad. Sci. U. S. A. 2003; PubMed Scopus Google Scholar). A negative regulatory binds the Sp1 N and binding with of Sp-dependent transcription (8Murata Y. Kim H.G. Rogers K.T. Udvadia A.J. Horowitz J.M. J. Biol. Chem. 1994; 269: 20674-20681Abstract Full Text PDF PubMed Google Scholar). has been determined that the and with the Sp1 N terminus J.A. Suh D.C. Kang J.E. Kim M.H. Park H. Lee M.N. Kim J.M. Jeon B.N. Roh H.E. Yu M.Y. Choi K.Y. Kim K.Y. Hur M.W. J. Biol. Chem. 2005; 280: 28061-28071Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar). is that SUMO-modified Sp1 has a affinity for Sp1 have been and an Sp1 a protein of amino acids S.P. S. PubMed Scopus Google Scholar). Sp1 may be explained by sites as has been to with which in A. F. G. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Udvadia A.J. Horowitz J.M. 1997; PubMed Scopus Google Scholar). acid analysis of the N terminus that a Sp1 N-terminal sumoylation site and N-terminal cleavage is that the first for and Sp1 may the of N-terminal SUMO-1-modified Sp This regulation be for since its the potential N-terminal sumoylation Sp1 is the model transcription factor for a large family of proteins and is the first mammalian transcription factor to be and there is to Sp1 gene regulatory that Sp1 be N-terminally cleaved in We Sp1 as a for SUMO-1 modification and that sumoylation may Sp1 transcription by the cleavage of a N-terminal negative regulatory domain. provide into the complexity of Sp-dependent gene regulation, the of sumoylation in Sp-dependent gene regulation, and a novel molecular mechanism the repressor function of Sp1 We and for their
Spengler et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: