Literature for peptidase T01.013: proteasome subunit beta1i

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates

(Topics flags: S Structure, A Assay, M Mutation, K Knockout, I Inhibitor, L Localization, V Review. To select only the references relevant to a single topic, click the link above. See explanation.)

    2024
  1. Arai,Y., Shitama,H., Yamagishi,M., Ono,S., Kashima,A., Hiraizumi,M., Tsuda,N., Katayama,K., Tanaka,K., Koda,Y., Kato,S., Sakata,K., Nureki,O. and Miyazaki,H.
    Optimization of alpha-amido boronic acids via cryo-electron microscopy analysis: Discovery of a novel highly selective immunoproteasome subunit LMP7 (beta5i)/LMP2 (beta1i) dual inhibitor
    Bioorg Med Chem109, 117790-117790. PubMed  Europe PubMed DOI  I
  2. Hu,X., Hu,Z., Zhang,H., Zhang,N., Feng,H., Jia,X., Zhang,C. and Cheng,Q.
    Deciphering the tumor-suppressive role of PSMB9 in melanoma through multi-omics and single-cell transcriptome analyses
    Cancer Lett581, 216466-216466. PubMed  Europe PubMed DOI
  3. 2023
  4. Elhawary,N.A., Ekram,S.N., Abumansour,I.S., Azher,Z.A., AlJahdali,I.A., Alyamani,N.M., Naffadi,H.M., Sindi,I.A., Baazeem,A., Nassir,A.M. and Mufti,A.H.
    Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma
    Cureus15, e36293-e36293. PubMed  Europe PubMed DOI
  5. Li,J., Hu,S., Johnson,H.W.B., Kirk,C.J., Xian,P., Song,Y., Li,Y., Liu,N., Groettrup,M. and Basler,M.
    Co-inhibition of immunoproteasome subunits LMP2 and LMP7 enables prevention of transplant arteriosclerosis
    Cardiovasc Res119, 1030-1045. PubMed  Europe PubMed DOI
  6. 2021
  7. Kanazawa,N., Hemmi,H., Kinjo,N., Ohnishi,H., Hamazaki,J., Mishima,H., Kinoshita,A., Mizushima,T., Hamada,S., Hamada,K., Kawamoto,N., Kadowaki,S., Honda,Y., Izawa,K., Nishikomori,R., Tsumura,M., Yamashita,Y., Tamura,S., Orimo,T., Ozasa,T., Kato,T., Sasaki,I., Fukuda-Ohta,Y., Wakaki-Nishiyama,N., Inaba,Y., Kunimoto,K., Okada,S., Taketani,T., Nakanishi,K., Murata,S., Yoshiura,K.I. and Kaisho,T.
    Heterozygous missense variant of the proteasome subunit beta-type 9 causes neonatal-onset autoinflammation and immunodeficiency
    Nat Commun12, 6819-6819. PubMed  Europe PubMed DOI
  8. 2020
  9. Bhattarai,D., Lee,M.J., Baek,A., Yeo,I.J., Miller,Z., Baek,Y.M., Lee,S., Kim,D.E., Hong,J.T. and Kim,K.B.
    LMP2 inhibitors as a potential treatment for Alzheimer's disease
    J Med Chem63, 3763-3783. PubMed  Europe PubMed DOI  I
  10. Ghannam,K., Martinez Gamboa,L., Kedor,C., Spengler,L., Kuckelkorn,U., Haupl,T., Burmester,G. and Feist,E.
    Response to abatacept is associated with the inhibition of proteasome beta1i expression in T cells of patients with rheumatoid arthritis
    RMD Open6, PubMed  Europe PubMed DOI
  11. Karim,M.R., Fisher,C.R., Kapphahn,R.J., Polanco,J.R. and Ferrington,D.A.
    Investigating AKT activation and autophagy in immunoproteasome-deficient retinal cells
    PLoS ONE15, e0231212-e0231212. PubMed  Europe PubMed DOI  K
  12. Li,C., Dai,S., Yan,Z., Zhang,X., Liu,S., Wang,X., Wang,J., Shi,L. and Yao,Y.
    Genetic polymorphisms of proteasome subunit genes of the MHC-I antigen-presenting system are associated with cervical cancer in a Chinese Han population
    Hum Immunol PubMed  Europe PubMed DOI  M
  13. Maurits,E., Degeling,C.G., Kisselev,A.F., Florea,B.I. and Overkleeft,H.S.
    Structure-Based Design of Fluorogenic Substrates Selective for Human Proteasome Subunits
    Chembiochem PubMed  Europe PubMed DOI
  14. Shirazi,F., Jones,R.J., Singh,R.K., Zou,J., Kuiatse,I., Berkova,Z., Wang,H., Lee,H.C., Hong,S., Dick,L., Chattopadhyay,N. and Orlowski,R.Z.
    Activating KRAS, NRAS, and BRAF mutants enhance proteasome capacity and reduce endoplasmic reticulum stress in multiple myeloma
    Proc Natl Acad Sci U S A117, 20004-20014. PubMed  Europe PubMed DOI
  15. 2019
  16. Allardyce,D.J., Bell,C.M. and Loizidou,E.Z.
    Argyrin B, a non-competitive inhibitor of the human immunoproteasome exhibiting preference for beta1i
    Chem Biol Drug Des94, 1556-1567. PubMed  Europe PubMed DOI  I
  17. Ettari,R., Cerchia,C., Maiorana,S., Guccione,M., Novellino,E., Bitto,A., Grasso,S., Lavecchia,A. and Zappala,M.
    Development of novel amides as noncovalent inhibitors of immunoproteasomes
    ChemMedChem14, 842-852. PubMed  Europe PubMed DOI  I
  18. Scarpino,A., Bajusz,D., Proj,M., Gobec,M., Sosic,I., Gobec,S., Ferenczy,G.G. and Keseru,G.M.
    Discovery of immunoproteasome inhibitors using large-scale covalent virtual screening
    Molecules24, PubMed  Europe PubMed DOI  I
  19. Sun,C., Mo,M., Wang,Y., Yu,W., Song,C., Wang,X., Chen,S. and Liu,Y.
    Activation of the immunoproteasome protects SH-SY5Y cells from the toxicity of rotenone
    Neurotoxicology73, 112-119. PubMed  Europe PubMed DOI
  20. Yeo,I.J., Lee,M.J., Baek,A., Miller,Z., Bhattarai,D., Baek,Y.M., Jeong,H.J., Kim,Y.K., Kim,D.E., Hong,J.T. and Kim,K.B.
    A dual inhibitor of the proteasome catalytic subunits LMP2 and Y attenuates disease progression in mouse models of Alzheimer's disease
    Sci Rep9, 18393-18393. PubMed  Europe PubMed DOI  I
  21. 2018
  22. Basler,M., Maurits,E., de Bruin,G., Koerner,J., Overkleeft,H.S. and Groettrup,M.
    Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome
    Br J Pharmacol175, 38-52. PubMed  Europe PubMed DOI  I
  23. Basler,M., Lindstrom,M.M., LaStant,J.J., Bradshaw,J.M., Owens,T.D., Schmidt,C., Maurits,E., Tsu,C., Overkleeft,H.S., Kirk,C.J., Langrish,C.L. and Groettrup,M.
    Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity
    EMBO Rep19, e46512-e46512. PubMed  Europe PubMed DOI  I
  24. Chen,X., Zhang,X., Chen,T., Jiang,X., Wang,X., Lei,H. and Wang,Y.
    Inhibition of immunoproteasome promotes angiogenesis via enhancing hypoxia-inducible factor-1alpha abundance in rats following focal cerebral ischaemia
    Brain Behav Immun73, 167-179. PubMed  Europe PubMed DOI  I
  25. Zanker,D., Pang,K., Oveissi,S., Lu,C., Faou,P., Nowell,C., Mbogo,G.W., Carotta,S., Quillici,C., Karupiah,G., Hibbs,M.L., Nutt,S.L., Neeson,P., Puthalakath,H. and Chen,W.
    LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins
    Immunol Cell Biol96, 981-993. PubMed  Europe PubMed DOI  K
  26. 2017
  27. Hewings,D.S., Flygare,J.A., Wertz,I.E. and Bogyo,M.
    Activity-based probes for the multicatalytic proteasome
    FEBS J284, 1540-1554. PubMed  Europe PubMed DOI  V  L  I
  28. Hovhannisyan,A.A., Pham,T.H., Bouvier,D., Tan,X., Touhar,S., Mkryan,G.G., Dallakyan,A.M., El Amri,C., Melikyan,G.S., Reboud-Ravaux,M. and Bouvier-Durand,M.
    Phenoxypropanolamine derivatives as selective inhibitors of the 20S proteasome beta1 and beta5 subunits
    Bioorg Med Chem Lett27, 5172-5178. PubMed  Europe PubMed DOI  I
  29. Johnson,H.W.B., Anderl,J.L., Bradley,E.K., Bui,J., Jones,J., Arastu-Kapur,S., Kelly,L.M., Lowe,E., Moebius,D.C., Muchamuel,T., Kirk,C., Wang,Z. and McMinn,D.
    Discovery of highly selective inhibitors of the immunoproteasome low molecular mass polypeptide 2 (LMP2) subunit
    ACS Med Chem Lett8, 413-417. PubMed  Europe PubMed DOI  I
  30. 2016
  31. de Bruin,G., Xin,B.T., Kraus,M., van der Stelt,M., van der Marel,G.A., Kisselev,A.F., Driessen,C., Florea,B.I. and Overkleeft,H.S.
    A set of activity-based probes to visualize human (immuno)proteasome activities
    Angew Chem Int Ed Engl55, 4199-4203. PubMed  Europe PubMed DOI  A  I
  32. Gvozdeva,O.V., Prassolov,V.S., Zenkova,M.A., Vlassov,V.V. and Chernolovskaya,E.L.
    Silencing of inducible immunoproteasome subunit expression by chemically modified siRNA and shRNA
    Nucleosides Nucleotides Nucleic Acids35, 389-403. PubMed  Europe PubMed DOI  K
  33. Kuzina,E.S., Kudriaeva,A.A., Maltseva,D.V. and Belogurov AA Jr
    Peptidyl aldehyde specifically interacts with immunosubunit beta1i proteasome: in vitro and in vivo effects
    Bull Exp Biol Med161, 69-71. PubMed  Europe PubMed DOI  I
  34. 2015
  35. Beilstein,F., Obiang,L., Raux,H. and Gaudin,Y.
    Characterization of the interaction between the matrix protein of vesicular stomatitis virus and the immunoproteasome subunit LMP2
    J Virol89, 11019-11029. PubMed  Europe PubMed DOI
  36. Brehm,A., Liu,Y., Sheikh,A., Marrero,B., Omoyinmi,E., Zhou,Q., Montealegre,G., Biancotto,A., Reinhardt,A., Almeida de Jesus,A., Pelletier,M., Tsai,W.L., Remmers,E.F., Kardava,L., Hill,S., Kim,H., Lachmann,H.J., Megarbane,A., Chae,J.J., Brady,J., Castillo,R.D., Brown,D., Casano,A.V., Gao,L., Chapelle,D., Huang,Y., Stone,D., Chen,Y., Sotzny,F., Lee,C.C., Kastner,D.L., Torrelo,A., Zlotogorski,A., Moir,S., Gadina,M., McCoy,P., Wesley,R., Rother,K., Hildebrand,P.W., Brogan,P., Kruger,E., Aksentijevich,I. and Goldbach-Mansky,R.
    Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production
    J Clin Invest125, 4196-4211. PubMed  Europe PubMed DOI  M
  37. 2014
  38. de Bruin,G., Huber,E.M., Xin,B.T., van Rooden,E.J., Al-Ayed,K., Kim,K.B., Kisselev,A.F., Driessen,C., van der Stelt,M., van der Marel,G.A., Groll,M. and Overkleeft,H.S.
    Structure-based design of beta1i or beta5i specific inhibitors of human immunoproteasomes
    J Med Chem57, 6197-6209. PubMed  Europe PubMed DOI  S  I
  39. Hovhannisyan,A., Pham,T.H., Bouvier,D., Piroyan,A., Dufau,L., Qin,L., Cheng,Y., Melikyan,G., Reboud-Ravaux,M. and Bouvier-Durand,M.
    New C(4)- and C(1)-derivatives of furo[3,4-c]pyridine-3-ones and related compounds: evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform
    Bioorg Med Chem Lett24, 1571-1580. PubMed  Europe PubMed DOI  I
  40. 2013
  41. Dechavanne,V., Vilbois,F., Glez,L. and Antonsson,B.
    Purification and separation of the 20S immunoproteasome from the constitutive proteasome and identification of the subunits by LC-MS
    Protein Expr Purif87, 100-110. PubMed  Europe PubMed DOI
  42. Miller,Z., Ao,L., Kim,K.B. and Lee,W.
    Inhibitors of the immunoproteasome: current status and future directions
    Curr Pharm Des19, 4140-4151. PubMed  Europe PubMed  I
  43. Park,J.E., Ao,L., Miller,Z., Kim,K., Wu,Y., Jang,E.R., Lee,E.Y., Kim,K.B. and Lee,W.
    PSMB9 codon 60 polymorphisms have no impact on the activity of the immunoproteasome catalytic subunit B1i expressed in multiple types of solid cancer
    PLoS ONE8, e73732-e73732. PubMed  Europe PubMed DOI
  44. Tacchi,L., Misra,M. and Salinas,I.
    Anti-viral immune responses in a primitive lung: Characterization and expression analysis of interferon-inducible immunoproteasome subunits LMP2, LMP7 and MECL-1 in a sarcopterygian fish, the Nigerian spotted lungfish (Protopterus dolloi)
    Dev Comp Immunol41, 657-665. PubMed  Europe PubMed DOI
  45. 2012
  46. Basler,M. and Groettrup,M.
    Immunoproteasome-specific inhibitors and their application
    Methods Mol Biol832, 391-401. PubMed  Europe PubMed DOI  I
  47. Basler,M., Lauer,C., Moebius,J., Weber,R., Przybylski,M., Kisselev,A.F., Tsu,C. and Groettrup,M.
    Why the structure but not the activity of the immunoproteasome subunit low molecular mass polypeptide 2 rescues antigen presentation
    J Immunol189, 1868-1877. PubMed  Europe PubMed DOI
  48. Grawert,M.A. and Groll,M.
    Eukaryotic 20S proteasome
    [ISSN:978-0-12-407742-3]3, 3684-3691. DOI
  49. Haroon,N., Maksymowych,W.P., Rahman,P., Tsui,F.W., O'Shea,F.D. and Inman,R.D.
    Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort
    Arthritis Rheum64, 1119-1126. PubMed  Europe PubMed DOI  M
  50. Wehenkel,M., Ban,J.O., Ho,Y.K., Carmony,K.C., Hong,J.T. and Kim,K.B.
    A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice
    Br J Cancer107, 53-62. PubMed  Europe PubMed DOI  I
  51. 2011
  52. Hayashi,T., Horiuchi,A., Sano,K., Hiraoka,N., Kasai,M., Ichimura,T., Nagase,S., Ishiko,O., Shiozawa,T., Kanai,Y., Yaegashi,N., Aburatani,H., Tonegawa,S. and Konishi,I.
    Involvement of proteasome beta1i subunit, LMP2, on development of uterin leiomyosarcma
    North Am J Med Sci3, 394-399. PubMed  Europe PubMed DOI
  53. Kuhn,D.J., Orlowski,R.Z. and Bjorklund,C.C.
    Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs)
    Curr Cancer Drug Targets11, 285-295. PubMed  Europe PubMed DOI  I
  54. Lee,W. and Kim,K.B.
    The immunoproteasome: an emerging therapeutic target
    Curr Top Med Chem11, 2923-2930. PubMed  Europe PubMed
  55. Sijts,E.J. and Kloetzel,P.M.
    The role of the proteasome in the generation of MHC class I ligands and immune responses
    Cell Mol Life Sci68, 1491-1502. PubMed  Europe PubMed DOI  V
  56. 2010
  57. Hayashi,T., Horiuchi,A., Sano,K., Hiraoka,N., Kanai,Y., Shiozawa,T., Tonegawa,S. and Konishi,I.
    Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma
    Protein Cell1, 711-717. PubMed  Europe PubMed DOI  K
  58. Lei,B., Abdul Hameed,M.D.M., Hamza,A., Wehenkel,M., Muzyka,J.L., Yao,X.J., Kim,K.B. and Zhan,C.G.
    Molecular basis of the selectivity of the immunoproteasome catalytic subunit LMP2-specific inhibitor revealed by molecular modeling and dynamics simulations
    J Phys Chem B114, 12333-12339. PubMed  Europe PubMed DOI  I
  59. 2009
  60. Kuhn,D.J., Hunsucker,S.A., Chen,Q., Voorhees,P.M., Orlowski,M. and Orlowski,R.Z.
    Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors
    Blood113, 4667-4676. PubMed  Europe PubMed DOI  I
  61. 2007
  62. Ho,Y.K., Bargagna-Mohan,P., Wehenkel,M., Mohan,R. and Kim,K.B.
    LMP2-Specific inhibitors: chemical genetic tools for proteasome biology
    Chem Biol14, 419-430. PubMed  Europe PubMed DOI  I
  63. 2006
  64. [YEAR:1-6-2006]Areste,C. and Blackbourn,D.J.
    HIV Tat-mediated transcriptional regulation of proteasome protein cleavage specificity
    Biochem J396, e13-e15. PubMed  Europe PubMed DOI
  65. Ding,Q., Martin,S., Dimayuga,E., Bruce-Keller,A.J. and Keller,J.N.
    LMP2 knock-out mice have reduced proteasome activities and increased levels of oxidatively damaged proteins
    Antioxid Redox Signal8, 130-135. PubMed  Europe PubMed DOI  K
  66. 2004
  67. [YEAR:15-9-2004]Basler,M., Youhnovski,N., Van Den Broek,M., Przybylski,M. and Groettrup,M.
    Immunoproteasomes down-regulate presentation of a subdominant T cell epitope from lymphocytic choriomeningitis virus
    J Immunol173, 3925-3934. PubMed  Europe PubMed
  68. Seemuller,E., Dolenc,I. and Lupas,A.
    Eukaryotic 20S proteasome
    [ISSN:0-12-079610-4]2, 2068-2077.  V
  69. 2003
  70. Kesmir,C., van Noort,V., de Boer,R.J. and Hogeweg,P.
    Bioinformatic analysis of functional differences between the immunoproteasome and the constitutive proteasome
    Immunogenetics55, 437-449. PubMed  Europe PubMed DOI
  71. Kruger,E., Kuckelkorn,U., Sijts,A. and Kloetzel,P.M.
    The components of the proteasome system and their role in MHC class I antigen processing
    Rev Physiol Biochem Pharmacol148, 81-104. PubMed  Europe PubMed DOI
  72. 2002
  73. [YEAR:15-9-2002]Singh,S., Awasthi,N., Egwuagu,C.E. and Wagner,B.J.
    Immunoproteasome expression in a nonimmune tissue, the ocular lens
    Arch Biochem Biophys405, 147-153. PubMed  Europe PubMed DOI
  74. Unno,M., Mizushima,T., Morimoto,Y., Tomisugi,Y., Tanaka,K., Yasuoka,N. and Tsukihara,T.
    The structure of the mammalian 20S proteasome at 2.75 A resolution
    Structure10, 609-618. PubMed  Europe PubMed DOI  S
  75. 2001
  76. [YEAR:2-7-2001]Toes,R.E., Nussbaum,A.K., Degermann,S., Schirle,M., Emmerich,N.P., Kraft,M., Laplace,C., Zwinderman,A., Dick,T.P., Muller,J., Schonfisch,B., Schmid,C., Fehling,H.J., Stevanovic,S., Rammensee,H.G. and Schild,H.
    Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products
    J Exp Med194, 1-12. PubMed  Europe PubMed DOI
  77. 2000
  78. [YEAR:15-10-2000]Clark,M.S., Pontarotti,P., Gilles,A., Kelly,A. and Elgar,G.
    Identification and characterization of a beta proteasome subunit cluster in the Japanese pufferfish (Fugu rubripes)
    J Immunol165, 4446-4452. PubMed  Europe PubMed
  79. [YEAR:4-8-2000]Kingsbury,D.J., Griffin,T.A. and Colbert,R.A.
    Novel propeptide function in 20 S proteasome assembly influences beta subunit composition
    J Biol Chem275, 24156-24162. PubMed  Europe PubMed DOI
  80. [YEAR:19-5-2000]Kisselev,A.F., Songyang,Z. and Goldberg,A.L.
    Why does threonine, and not serine, function as the active site nucleophile in proteasomes?
    J Biol Chem275, 14831-14837. PubMed  Europe PubMed DOI  I
  81. [YEAR:15-7-2000]Schwarz,K., Van Den Broek,M., Kostka,S., Kraft,R., Soza,A., Schmidtke,G., Kloetzel,P.M. and Groettrup,M.
    Overexpression of the proteasome subunits LMP2, LMP7, and MECL-1, but not PA28alpha/beta, enhances the presentation of an immunodominant lymphocytic choriomeningitis virus T cell epitope
    J Immunol165, 768-778. PubMed  Europe PubMed
  82. 1998
  83. [YEAR:5-1-1998]Griffin,T.A., Nandi,D., Cruz,M., Fehling,H.J., Van Kaer,L., Monaco,J.J. and Colbert,R.A.
    Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits
    J Exp Med187, 97-104. PubMed  Europe PubMed DOI
  84. 1997
  85. Eleuteri,A.M., Kohanski,R.A., Cardozo,C. and Orlowski,M.
    Bovine spleen multicatalytic proteinase complex (proteasome). Replacement of X, Y, and Z subunits by LMP7, LMP2, and MECL1 and changes in properties and specificity
    J Biol Chem272, 11824-11831. PubMed  Europe PubMed DOI
  86. Hughes,A.L.
    Evolution of the proteasome components
    Immunogenetics46, 82-92. PubMed  Europe PubMed DOI
  87. Nonaka,M., Namikawa-Yamada,C., Sasaki,M., Salter-Cid,L. and Flajnik,M.F.
    Evolution of proteasome subunits delta and LMP2: complementary DNA cloning and linkage analysis with MHC in lower vertebrates
    J Immunol159, 734-740. PubMed  Europe PubMed
  88. 1996
  89. Coux,O., Tanaka,K. and Goldberg,A.L.
    Structure and functions of the 20S and 26S proteasomes
    Annu Rev Biochem65, 801-847. PubMed  Europe PubMed DOI
  90. 1995
  91. [YEAR:6-10-1995]Groettrup,M., Ruppert,T., Kuehn,L., Seeger,M., Standera,S., Koszinowski,U. and Kloetzel,P.M.
    The interferon-gamma-inducible 11 S regulator (PA28) and the LMP2/LMP7 subunits govern the peptide production by the 20 S proteasome in vitro
    J Biol Chem270, 23808-23815. PubMed  Europe PubMed DOI
  92. Sibille,C., Gould,K.G., Willard-Gallo,K., Thomson,S., Rivett,A.J., Powis,S., Butcher,G.W. and De Baetselier,P.
    LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes
    Curr Biol5, 923-930. PubMed  Europe PubMed  K
  93. Woodward,E.C. and Monaco,J.J.
    Characterization and mapping of the gene encoding mouse proteasome subunit DELTA (Lmp19)
    Immunogenetics42, 28-34. PubMed  Europe PubMed DOI