Leta i den här bloggen


tisdag 8 maj 2018

TRIM33 rakenne isoformi alfa



Rakenne. Konservoidut domeenit. Löydän isoformit alfa (1127 aa), beta (1110 aa), X2 (1150 aa) , X3 (1134 aa) , X1 (1151 aa) , X5 (609 aa). Muissa on samat mainitut konservoidut domeenit paitis tuossa lyhyessä on jakso nimeltä atrophin.
Otan tähän konservoidut domeenit isoformista alfa, joka on ensinmainittu.
cd05502
Location:958 → 1083
Bromo_tif1_like; Bromodomain; tif1_like subfamily. Tif1 (transcription intermediary factor 1) is a member of the tripartite motif (TRIM) protein family, which is characterized by a particular domain architecture. It functions by recruiting coactivators and/or corepressors to modulate transcription. Vertebrate Tif1-gamma, also labeled E3 ubiquitin-protein ligase TRIM33, plays a role in the control of hematopoiesis. Its homologue in Xenopus laevis, Ectodermin, has been shown to function in germ-layer specification and control of cell growth during embryogenesis. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.
smart00502
Location:319 → 445
BBC; B-Box C-terminal domain
smart00336
Location:212 → 248
BBOX; B-Box-type zinc finger
cd00021
Location:274 → 312
BBOX; B-Box-type zinc finger; zinc binding domain (CHC3H2); often present in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interaction.
cd00162
Location:124 → 188
RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
cd15624
Location:889 → 934
PHD_TIF1gamma; PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma)
TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.
---------------------------------------------------

(Otan muistiin tuon atrofiini-1 pätkän merkityksen. Vähän vehnäsen näköinen, paljon q ja p.
Isoformista x5 Atrophin-1 family
  • Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity).

Tavallinen isoformi alfa:

GenPept

E3 ubiquitin-protein ligase TRIM33 isoform alpha [Homo sapiens]

NCBI Reference Sequence: NP_056990.3

Identical Proteins FASTA Graphics

LOCUS       NP_056990               1127 aa            linear   PRI 08-APR-2018
DEFINITION  E3 ubiquitin-protein ligase TRIM33 isoform alpha [Homo sapiens].
ACCESSION   NP_056990
VERSION     NP_056990.3
DBSOURCE    REFSEQ: accession NM_015906.3
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1127)
  AUTHORS   Yin X, Xu C, Zheng X, Yuan H, Liu M, Qiu Y and Chen J.
  TITLE     SnoN suppresses TGF-beta-induced epithelial-mesenchymal transition
            and invasion of bladder cancer in a TIF1gamma-dependent manner
  JOURNAL   Oncol. Rep. 36 (3), 1535-1541 (2016)
   PUBMED   27430247
  REMARK    GeneRIF: suggest that SnoN suppresses TGF-betainduced
            epithelial-mesenchymal transition and invasion of bladder cancer
            cells in a TIF1gammadependent manner
REFERENCE   2  (residues 1 to 1127)
  AUTHORS   Shi X, Mihaylova VT, Kuruvilla L, Chen F, Viviano S, Baldassarre M,
            Sperandio D, Martinez R, Yue P, Bates JG, Breckenridge DG,
            Schlessinger J, Turk BE and Calderwood DA.
  TITLE     Loss of TRIM33 causes resistance to BET bromodomain inhibitors
            through MYC- and TGF-beta-dependent mechanisms
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 113 (31), E4558-E4566 (2016)
   PUBMED   27432991
  REMARK    GeneRIF: Data show that tripartite motif-containing protein 33
            (TRIM33) silencing attenuates down-regulation of MYC and TGF-beta
            signaling in response to bromodomain and extraterminal domain
            protein inhibitors (BETi).
REFERENCE   3  (residues 1 to 1127)
  AUTHORS   Sohn SY and Hearing P.
  TITLE     The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for
            TIF-1gamma sumoylation and poly-SUMO chain elongation
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 113 (24), 6725-6730 (2016)
   PUBMED   27247387
  REMARK    GeneRIF: The adenovirus E4-ORF3 protein functions as a SUMO E3
            ligase for TIF-1gamma sumoylation and poly-SUMO chain elongation.
REFERENCE   4  (residues 1 to 1127)
  AUTHORS   Wang L, Yang H, Lei Z, Zhao J, Chen Y, Chen P, Li C, Zeng Y, Liu Z,
            Liu X and Zhang HT.
  TITLE     Repression of TIF1gamma by SOX2 promotes TGF-beta-induced
            epithelial-mesenchymal transition in non-small-cell lung cancer
  JOURNAL   Oncogene 35 (7), 867-877 (2016)
   PUBMED   25961934
  REMARK    GeneRIF: our findings reveal a new mechanism by which SOX2-mediated
            transcription repression of TIF1gamma promotes TGF-beta-induced
            epithelial-mesenchymal transition in non-small-cell lung cancer
REFERENCE   5  (residues 1 to 1127)
  AUTHORS   Pommier RM, Gout J, Vincent DF, Alcaraz LB, Chuvin N, Arfi V,
            Martel S, Kaniewski B, Devailly G, Fourel G, Bernard P,
            Moyret-Lalle C, Ansieau S, Puisieux A, Valcourt U, Sentis S and
            Bartholin L.
  TITLE     TIF1gamma Suppresses Tumor Progression by Regulating Mitotic
            Checkpoints and Chromosomal Stability
  JOURNAL   Cancer Res. 75 (20), 4335-4350 (2015)
   PUBMED   26282171
  REMARK    GeneRIF: our work indicates that TIF1gamma exerts its
            tumor-suppressive functions in part by promoting chromosomal
            stability.
REFERENCE   6  (residues 1 to 1127)
  AUTHORS   He W, Dorn DC, Erdjument-Bromage H, Tempst P, Moore MA and Massague
            J.
  TITLE     Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches
            of the TGFbeta pathway
  JOURNAL   Cell 125 (5), 929-941 (2006)
   PUBMED   16751102
  REMARK    GeneRIF: Thus, Smad2/3-TIF1gamma and Smad2/3-Smad4 function as
            complementary effector arms in the control of hematopoietic cell
            fate by the TGFbeta/Smad pathway.
REFERENCE   7  (residues 1 to 1127)
  AUTHORS   Peng H, Feldman I and Rauscher FJ 3rd.
  TITLE     Hetero-oligomerization among the TIF family of RBCC/TRIM
            domain-containing nuclear cofactors: a potential mechanism for
            regulating the switch between coactivation and corepression
  JOURNAL   J. Mol. Biol. 320 (3), 629-644 (2002)
   PUBMED   12096914
  REMARK    GeneRIF: TIF1alpha interacts with TIF1gamma and the coiled-coil
            region of TIF1gamma is necessary for this inteactrion.
REFERENCE   8  (residues 1 to 1127)
  AUTHORS   Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L,
            Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci
            S, Pelicci PG and Ballabio A.
  TITLE     The tripartite motif family identifies cell compartments
  JOURNAL   EMBO J. 20 (9), 2140-2151 (2001)
   PUBMED   11331580
REFERENCE   9  (residues 1 to 1127)
  AUTHORS   Klugbauer S and Rabes HM.
  TITLE     The transcription coactivator HTIF1 and a related protein are fused
            to the RET receptor tyrosine kinase in childhood papillary thyroid
            carcinomas
  JOURNAL   Oncogene 18 (30), 4388-4393 (1999)
   PUBMED   10439047
REFERENCE   10 (residues 1 to 1127)
  AUTHORS   Venturini L, You J, Stadler M, Galien R, Lallemand V, Koken MH,
            Mattei MG, Ganser A, Chambon P, Losson R and de The H.
  TITLE     TIF1gamma, a novel member of the transcriptional intermediary
            factor 1 family
  JOURNAL   Oncogene 18 (5), 1209-1217 (1999)
   PUBMED   10022127
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CN267696.1, AF119043.1,
            AB029036.1, AK023434.1 and AL035410.7.
            This sequence is a reference standard in the RefSeqGene project.
            On Aug 31, 2005 this sequence version replaced NP_056990.2.
            
            Summary: The protein encoded by this gene is thought to be a
            transcriptional corepressor. However, molecules that interact with
            this protein have not yet been identified. The protein is a member
            of the tripartite motif family. This motif includes three
            zinc-binding domains, a RING, a B-box type 1 and a B-box type 2,
            and a coiled-coil region. Three alternatively spliced transcript
            variants for this gene have been described, however, the
            full-length nature of one variant has not been determined.
            [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (a) encodes the longer isoform
            (alpha).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF119043.1, AF220136.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..1127
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p13.2"
     Protein         1..1127
                     /product="E3 ubiquitin-protein ligase TRIM33 isoform
                     alpha"
                     /EC_number="2.3.2.27"
                     /note="transcriptional intermediary factor 1 gamma; E3
                     ubiquitin-protein ligase TRIM33; TIF1-gamma; protein Rfg7;
                     ectodermin homolog; RET-fused gene 7 protein; RING-type E3
                     ubiquitin transferase TRIM33"
                     /calculated_mol_wt=122403
     Region          1..147
                     /region_name="Necessary for E3 ubiquitin-protein ligase
                     activity and repression of SMAD4 signaling and
                     transcriptional repression"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Region          124..188
                     /region_name="RING"
                     /note="RING-finger (Really Interesting New Gene) domain, a
                     specialized type of Zn-finger of 40 to 60 residues that
                     binds two atoms of zinc; defined by the 'cross-brace'
                     motif C-X2-C-X(9-39)-C-X(1-3)-
                     H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved
                     in...; cd00162"
                     /db_xref="CDD:238093"
     Site            order(125,128,145,147,150,153,181,184)
                     /site_type="other"
                     /note="cross-brace motif"
                     /db_xref="CDD:238093"
     Region          212..248
                     /region_name="BBOX"
                     /note="B-Box-type zinc finger; smart00336"
                     /db_xref="CDD:197662"
     Region          274..312
                     /region_name="BBOX"
                     /note="B-Box-type zinc finger; zinc binding domain
                     (CHC3H2); often present in combination with other motifs,
                     like RING zinc finger, NHL motif, coiled-coil or RFP
                     domain in functionally unrelated proteins, most likely
                     mediating protein-protein interaction; cd00021"
                     /db_xref="CDD:237988"
     Site            order(276,279,299,304)
                     /site_type="other"
                     /note="Zn2+ binding site [ion binding]"
                     /db_xref="CDD:237988"
     Region          299..401
                     /region_name="Necessary for oligomerization"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Region          319..445
                     /region_name="BBC"
                     /note="B-Box C-terminal domain; smart00502"
                     /db_xref="CDD:128778"
     Site            515
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Asymmetric dimethylarginine, alternate.
                     {ECO:0000244|PubMed:24129315}; Omega-N-methylarginine,
                     alternate. {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            535
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Omega-N-methylarginine.
                     {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            577
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Asymmetric dimethylarginine.
                     {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            591
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Asymmetric dimethylarginine, alternate.
                     {ECO:0000250|UniProtKB:Q99PP7}; Omega-N-methylarginine,
                     alternate. {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            598
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Asymmetric dimethylarginine.
                     {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            604
                     /site_type="methylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Asymmetric dimethylarginine.
                     {ECO:0000244|PubMed:24129315}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            763
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine, alternate.
                     {ECO:0000244|PubMed:19608861}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            769
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine, alternate.
                     {ECO:0000244|PubMed:19608861}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            793
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine, alternate.
                     {ECO:0000250|UniProtKB:Q99PP7}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            803
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q99PP7};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            815
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphothreonine. {ECO:0000250|UniProtKB:Q99PP7};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            862
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:21406692,
                     ECO:0000244|PubMed:23186163}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Region          889..934
                     /region_name="PHD_TIF1gamma"
                     /note="PHD finger found in transcriptional intermediary
                     factor 1 gamma (TIF1gamma); cd15624"
                     /db_xref="CDD:277094"
     Site            order(889,894..895,898..903,910,923..924)
                     /site_type="other"
                     /note="histone H3 binding site [polypeptide binding]"
                     /db_xref="CDD:277094"
     Site            order(890,893,902,905,910,913,928,931)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:277094"
     Site            951
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000250|UniProtKB:Q99PP7};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            953
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine, alternate.
                     {ECO:0000244|PubMed:19608861}; propagated from
                     UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Region          958..1083
                     /region_name="Bromo_tif1_like"
                     /note="Bromodomain; tif1_like subfamily. Tif1
                     (transcription intermediary factor 1) is a member of the
                     tripartite motif (TRIM) protein family, which is
                     characterized by a particular domain architecture. It
                     functions by recruiting coactivators and/or...; cd05502"
                     /db_xref="CDD:99934"
     Site            964..965
                     /site_type="other"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Breakpoint for translocation to form TRIM33-RET
                     oncogene; propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            order(986,990,993,1035,1039,1062)
                     /site_type="other"
                     /note="putative acetyllysine binding site [chemical
                     binding]"
                     /db_xref="CDD:99934"
     Site            1051
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphothreonine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            1102
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphothreonine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:21406692};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            1105
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:21406692};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     Site            1119
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q9UPN9.3)"
     CDS             1..1127
                     /gene="TRIM33"
                     /gene_synonym="ECTO; PTC7; RFG7; TF1G; TIF1G; TIF1GAMMA;
                     TIFGAMMA"
                     /coded_by="NM_015906.3:85..3468"
                     /note="isoform alpha is encoded by transcript variant a"
                     /db_xref="CCDS:CCDS872.1"
                     /db_xref="GeneID:51592"
                     /db_xref="HGNC:HGNC:16290"
                     /db_xref="MIM:605769"
ORIGIN      
        1 maenkgggea esggggsgsa pvtagaagpa aqeaepplta vlveeeeeeg gragaeggaa
       61 gpddggvaaa ssgsaqaass paasvgtgva ggavstpapa pasapapgps agpppgppas
      121 lldtcavcqq slqsrreaep kllpclhsfc lrclpeperq lsvpipggsn gdiqqvgvir
      181 cpvcrqecrq idlvdnyfvk dtseapsssd ekseqvctsc ednasavgfc vecgewlckt
      241 cieahqrvkf tkdhlirkke dvsesvgasg qrpvfcpvhk qeqlklfcet cdrltcrdcq
      301 llehkehryq fleeafqnqk gaienllakl lekknyvhfa atqvqnrike vnetnkrveq
      361 eikvaiftli neinkkgksl lqqlenvtke rqmkllqqqn ditglsrqvk hvmnftnwai
      421 asgsstally skrlitfqlr hilkarcdpv paangairfh cdptfwaknv vnlgnlvies
      481 kpapgytpnv vvgqvppgtn hisktpgqin laqlrlqhmq qqvyaqkhqq lqqmrmqqpp
      541 apvptttttt qqhprqaapq mlqqqpprli svqtmqrgnm ncgafqahqm rlaqnaarip
      601 giprhsgpqy smmqphlqrq hsnpghagpf pvvsvhntti nptspttatm ananrgptsp
      661 svtaielips vtnpenlpsl pdippiqled agsssldnll sryisgshlp pqptstmnps
      721 pgpsalspgs sglsnshtpv rppstsstgs rgscgssgrt aektslsfks dqvkvkqepg
      781 tedeicsfsg gvkqektedg rrsacmlssp essltpplst nlhleselda laslenhvki
      841 epadmnesck qsglsslvng kspirslmhr sariggdgnn kdddpnedwc avcqnggdll
      901 ccekcpkvfh ltchvptlls fpsgdwictf crdigkpeve ydcdnlqhsk kgktaqglsp
      961 vdqrkcerll lylychelsi efqepvpasi pnyykiikkp mdlstvkkkl qkkhsqhyqi
     1021 pddfvadvrl ifkncerfne mmkvvqvyad tqeinlkads evaqagkava lyfedkltei
     1081 ysdrtfaplp efeqeeddge vtedsdedfi qprrkrlksd erpvhik
//




Related articles in PubMed

  1. The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation. Sohn SY, et al. Proc Natl Acad Sci U S A, 2016 Jun 14. PMID 27247387, Free PMC Article The E4-ORF3 protein displays no SUMO-targeted ubiquitin ligase activity in our assay system. These studies reveal the mechanism by which E4-ORF3 targets specific cellular proteins for sumoylation and proteasomal degradation and provide significant insight into how a small viral protein can play a role as a SUMO E3 ligase and E4-like SUMO elongase to impact a variety of cellular responses.
See all (71) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Bromodomain and extraterminal domain protein inhibitors (BETi) hold great promise as a novel class of cancer therapeutics. Because acquired resistance typically limits durable responses to targeted therapies, it is important to understand mechanisms by which tumor cells adapt to BETi. Here, through pooled shRNA screening of colorectal cancer cells, we identified tripartite motif-containing protein 33 (TRIM33) as a factor promoting sensitivity to BETi. We demonstrate that loss of TRIM33 reprograms cancer cells to a more resistant state through at least two mechanisms. TRIM33 silencing attenuates down-regulation of MYC in response to BETi. Moreover, loss of TRIM33 enhances TGF-β receptor expression and signaling, and blocking TGF-β receptor activity potentiates the antiproliferative effect of BETi. These results describe a mechanism for BETi resistance and suggest that combining inhibition of TGF-β signaling with BET bromodomain inhibition may offer new therapeutic benefits.




Inga kommentarer:

Skicka en kommentar