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Literature for peptidase S14.003: peptidase Clp (type 3)

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

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

    2025
  1. Goncalves,M.M., Uday,A.B., Forrester,T.J.B., Currie,S.Q.W., Kim,A.S., Feng,Y., Jitkova,Y., Velyvis,A., Harkness,R.W., Kimber,M.S., Schimmer,A.D., Zeytuni,N. and Vahidi,S.
    Mechanism of allosteric activation in human mitochondrial ClpP protease
    Proc Natl Acad Sci U S A122, e2419881122-e2419881122. PubMed  Europe PubMed DOI  I
  2. Liu,X., Gu,J., Liu,S., Huang,J., Li,L., Wang,F., He,S., Mi,Z., Zhang,Y., Wen,J., Gao,Q., Yang,H., Feng,Y., Luo,H., Zhai,X., Zhang,L., Zheng,Y., Luo,Y. and Niu,T.
    The mitochondrial protease ClpP is a promising target for multiple myeloma treatment
    Biochem Pharmacol236, 116855-116855. PubMed  Europe PubMed DOI  I
  3. Perini,T., Zordan,P., Del Pizzo,R., Resnati,M., Viviani,L., Stefanoni,D., Cassina,L., Orfanelli,U.P., Trudu,M., Oliva,L., Lacidogna,D., Samur,M.K., Materozzi,M., Drago,D., Andolfo,A., Patrone,M., Degano,M., Boletta,A., Milan,E., Ciceri,F., Munshi,N.C., Bellone,M. and Cenci,S.
    The mitochondrial protease ClpP is a metabolic vulnerability and an immunogenic trigger against multiple myeloma
    Blood PubMed  Europe PubMed DOI
  4. Qin,L., Moreno Rueda,L.Y., Ray,U., Mahmud,I., Tan,L., Lorenzi,P.L., Liu,S., Lin,H.Y., Mery,D.E., Zhan,F., Shaughnessy,J.D., Jr., Yi,Q., Acevedo Calado,M.J., Wang,H., Manasanch,E.E., Lee,H.C., Patel,K.K., Kuiatse,I., Symer,D.E. and Orlowski,R.Z.
    Targeting Caseinolytic Mitochondrial Matrix Peptidase, a Novel Contributor to High-risk Behavior, in Multiple Myeloma
    Blood PubMed  Europe PubMed DOI
  5. Tang,R., Li,Q., Zhou,H., Li,Y., Li,T., Jiang,J., Chen,Z., Kong,L., Li,Y., Xiao,Y. and Sun,H.
    Design, Synthesis, and Biological Evaluation of Novel Activators of Human Caseinolytic Protease P with a Pyrazololactam Scaffold
    J Med Chem PubMed  Europe PubMed DOI
  6. Tserennadmid,B., Nam,M.K., Park,J.H., Rhim,H. and Kang,S.
    HAP/ClpP-mediated disaggregation and degradation of Mutant SOD1 aggregates: A potential therapeutic strategy for Amyotrophic lateral sclerosis (ALS)
    Biochem Biophys Res Commun756, 151533-151533. PubMed  Europe PubMed DOI
    7. 2024
  7. Cao,J., Cao,F., Wang,C., Jiao,Z., You,Y., Wang,X. and Zhao,W.
    ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells
    Neoplasia55, 101015-101015. PubMed  Europe PubMed DOI  K  I
  8. Giarrizzo,M., LaComb,J.F., Patel,H.R., Reddy,R.G., Haley,J.D., Graves,L.M., Iwanowicz,E.J. and Bialkowska,A.B.
    TR-107, An Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
    Mol Cancer Ther23, 1761-1778. PubMed  Europe PubMed DOI
  9. Jiang,J., Xie,G., Li,T., Ding,H., Tang,R., Luo,J., Li,Q., Lu,W., Xiao,Y. and Sun,H.
    Discovery of Dehydrogenated Imipridone Derivatives as Activators of Human Caseinolytic Protease P
    J Med Chem67, 15328-15352. PubMed  Europe PubMed DOI  I
  10. Liu,S., Sui,J., Luo,B., Zhang,J., Xiang,X., Yang,T., Luo,Y. and Liu,J.
    Discovery of 5-(Piperidin-4-yl)-1,2,4-oxadiazole Derivatives as a New Class of Human Caseinolytic Protease P Agonists for the Treatment of Hepatocellular Carcinoma
    J Med Chem PubMed  Europe PubMed DOI  I
  11. Miciaccia,M., Rizzo,F., Centonze,A., Cavallaro,G., Contino,M., Armenise,D., Baldelli,O.M., Solidoro,R., Ferorelli,S., Scarcia,P., Agrimi,G., Zingales,V., Cimetta,E., Ronsisvalle,S., Sipala,F.M., Polosa,P.L., Fortuna,C.G., Perrone,M.G. and Scilimati,A.
    Harmaline to Human Mitochondrial Caseinolytic Serine Protease Activation for Pediatric Diffuse Intrinsic Pontine Glioma Treatment
    Pharmaceuticals (Basel)17, PubMed  Europe PubMed DOI  I
  12. Paredes,F., Williams,H.C., Liu,X., Holden,C., Bogan,B., Wang,Y., Crotty,K.M., Yeligar,S.M., Elorza,A.A., Lin,Z., Rezvan,A. and San Martin,A.
    The mitochondrial protease ClpP is a druggable target that controls VSMC phenotype by a SIRT1-dependent mechanism
    Redox Biol73, 103203-103203. PubMed  Europe PubMed DOI
  13. Zhang,J., Qiu,Z., Liu,S., Huang,J., Luo,B., Sui,J., Dai,Z., Xiang,X., Yang,T. and Luo,Y.
    Discovery of a Novel Series of Homo sapiens Caseinolytic Protease P Agonists for Colorectal Adenocarcinoma Treatment via ATF3-Dependent Integrated Stress Response
    J Med Chem67, 2812-2836. PubMed  Europe PubMed DOI
    14. 2023
  14. Gonzalez-Paz,L., Lossada,C., Hurtado-Leon,M.L., Fernandez-Materan,F.V., Paz,J.L., Parvizi,S., Cardenas Castillo,R.E., Romero,F. and Alvarado,Y.J.
    Intrinsic Dynamics of the ClpXP Proteolytic Machine Using Elastic Network Models
    ACS Omega8, 7302-7318. PubMed  Europe PubMed DOI
  15. Guo,C., Xiao,Y., Gu,J., Zhao,P., Hu,Z., Zheng,J., Hua,R., Hai,Z., Su,J., Zhang,J.V., Yeung,W.S.B. and Wang,T.
    ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis
    Commun Biol6, 1012-1012. PubMed  Europe PubMed DOI
  16. Zhang,R., Wang,P., Wei,B., Chen,L., Song,X., Pan,Y., Li,J., Gan,J., Zhang,T. and Yang,C.G.
    Assessment of the structure-activity relationship and antileukemic activity of diacylpyramide compounds as human ClpP agonists
    Eur J Med Chem258, 115577-115577. PubMed  Europe PubMed DOI
    17. 2022
  17. Huang,J., Zhang,J., Luo,B., Qiao,W., Qiu,Z., Song,R., Dai,Z., Sui,J., Xu,X., Ruan,S., Li,C., Luo,Y. and Yang,T.
    Discovery of a Novel Series of Imipridone Compounds as Homo sapiens Caseinolytic Protease P Agonists with Potent Antitumor Activities In Vitro and In Vivo
    J Med Chem65, 7629-7655. DOI
  18. Wang,P., Zhang,T., Wang,X., Xiao,H., Li,H., Zhou,L.L., Yang,T., Wei,B., Zhu,Z., Zhou,L., Yang,S., Lu,X., Zhang,Y., Huang,Y., Gan,J. and Yang,C.G.
    Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma
    Cell Chem Biol29, 1396-1408. PubMed  Europe PubMed DOI
  19. Zhang,J., Luo,B., Sui,J., Qiu,Z., Huang,J., Yang,T. and Luo,Y.
    IMP075 targeting ClpP for colon cancer therapy in vivo and in vitro
    Biochem Pharmacol204, 115232-115232. PubMed  Europe PubMed DOI  K
    20. 2021
  20. Cormio,A., Sanguedolce,F., Pesce,V. and Musicco,C.
    Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer
    Int J Mol Sci22, PubMed  Europe PubMed DOI  V
  21. Forli,F., Bruschini,L., Franciosi,B., Battini,R., Marinella,G., Berrettini,S. and Lazzerini,F.
    A Rare Case of Perrault Syndrome with Auditory Neuropathy Spectrum Disorder: Cochlear Implantation Treatment and Literature Review
    Audiol Res11, 609-617. PubMed  Europe PubMed DOI
  22. Kou,X., Ding,H., Li,L. and Chao,H.
    Caseinolytic protease P (CLPP) activated by ONC201 inhibits proliferation and promotes apoptosis in human epithelial ovarian cancer cells by inducing mitochondrial dysfunction
    Ann Transl Med9, 1463-1463. PubMed  Europe PubMed DOI
  23. Song,R., Yang,Y., Huang,J., Qiao,W., Luo,B., Ju,Y., Yang,T. and Luo,Y.
    Discovery of novel indolin-2-one compounds as potent inhibitors of HsClpP for cancer treatment
    Bioorg Chem110, 104820-104820. PubMed  Europe PubMed DOI  I
    24. 2020
  24. Esencan,E., Cozzolino,M., Imamoglu,G. and Seli,E.
    Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function
    Antioxidants (Basel)10, PubMed  Europe PubMed DOI
  25. Esencan,E., Jiang,Z., Wang,T., Zhang,M., Soylemez-Imamoglu,G. and Seli,E.
    Impaired mitochondrial stress response due to CLPP deletion is associated with altered mitochondrial dynamics and increased apoptosis in cumulus cells
    Reprod Sci27, 621-630. PubMed  Europe PubMed DOI  K
  26. Jacques,S., van der Sloot,A.M., C Huard,C., Coulombe-Huntington,J., Tsao,S., Tollis,S., Bertomeu,T., Culp,E.J., Pallant,D., Cook,M.A., Bonneil,E., Thibault,P., Wright,G.D. and Tyers,M.
    Imipridone anticancer compounds ectopically activate the ClpP protease and represent a new scaffold for antibiotic development
    Genetics214, 1103-1120. PubMed  Europe PubMed DOI
  27. Mirali,S. and Schimmer,A.D.
    The role of mitochondrial proteases in leukemic cells and leukemic stem cells
    Stem Cells Transl Med PubMed  Europe PubMed DOI
  28. Nouri,K., Feng,Y. and Schimmer,A.D.
    Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy
    Cell Death Dis11, 841-841. PubMed  Europe PubMed DOI  V
  29. Prabhu,V.V., Morrow,S., Rahman Kawakibi,A., Zhou,L., Ralff,M., Ray,J., Jhaveri,A., Ferrarini,I., Lee,Y., Parker,C., Zhang,Y., Borsuk,R., Chang,W.I., Honeyman,J.N., Tavora,F., Carneiro,B., Raufi,A., Huntington,K., Carlsen,L., Louie,A., Safran,H., Seyhan,A.A., Tarapore,R.S., Schalop,L., Stogniew,M., Allen,J.E., Oster,W. and El-Deiry,W.S.
    ONC201 and imipridones: Anti-cancer compounds with clinical efficacy
    Neoplasia22, 725-744. PubMed  Europe PubMed DOI
  30. Ripstein,Z.A., Vahidi,S., Houry,W.A., Rubinstein,J.L. and Kay,L.E.
    A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery
    elife9, PubMed  Europe PubMed DOI  S
  31. Sha,Z., Fishovitz,J., Wang,S., Chilakala,S., Xu,Y. and Lee,I.
    A selective fluorogenic peptide substrate for the human mitochondrial ATP-dependent protease complex ClpXP
    Chembiochem21, 2037-2048. PubMed  Europe PubMed DOI  A  P  I
  32. Strack,P.R., Brodie,E.J., Zhan,H., Schuenemann,V.J., Valente,L.J., Saiyed,T., Lowth,B.R., Angley,L.M., Perugini,M.A., Zeth,K., Truscott,K.N. and Dougan,D.A.
    Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP
    Commun Biol3, 646-646. PubMed  Europe PubMed DOI
    33. 2019
  33. Ishizawa,J., Zarabi,S.F., Davis,R.E., Halgas,O., Nii,T., Jitkova,Y., Zhao,R., St-Germain,J., Heese,L.E., Egan,G., Ruvolo,V.R., Barghout,S.H., Nishida,Y., Hurren,R., Ma,W., Gronda,M., Link,T., Wong,K., Mabanglo,M., Kojima,K., Borthakur,G., Maclean,N., Ma,M.C.J., Leber,A.B., Minden,M.D., Houry,W., Kantarjian,H., Stogniew,M., Raught,B., Pai,E.F., Schimmer,A.D. and Andreeff,M.
    Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality
    Cancer Cell35, 721-737. PubMed  Europe PubMed DOI
  34. Wong,K.S. and Houry,W.A.
    Chemical modulation of human mitochondrial ClpP: potential application in cancer therapeutics
    ACS Chem Biol14, 2349-2360. PubMed  Europe PubMed DOI
    35. 2018
  35. Becker,C., Kukat,A., Szczepanowska,K., Hermans,S., Senft,K., Brandscheid,C.P., Maiti,P. and Trifunovic,A.
    CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis
    EMBO Rep19, e45126.-e45126. PubMed  Europe PubMed DOI
  36. Bhaskaran,S., Pharaoh,G., Ranjit,R., Murphy,A., Matsuzaki,S., Nair,B.C., Forbes,B., Gispert,S., Auburger,G., Humphries,K.M., Kinter,M., Griffin,T.M. and Deepa,S.S.
    Loss of mitochondrial protease ClpP protects mice from diet-induced obesity and insulin resistance
    EMBO Rep19, e45009-e45009. PubMed  Europe PubMed DOI  K
  37. Brodie,E.J., Zhan,H., Saiyed,T., Truscott,K.N. and Dougan,D.A.
    Perrault syndrome type 3 caused by diverse molecular defects in CLPP
    Sci Rep8, 12862-12862. PubMed  Europe PubMed DOI  M
  38. Dougan,D.A., Hantke,I. and Turgay,K.
    Dysregulating ClpP: from antibiotics to anticancer?
    Cell Chem Biol25, 929-930. PubMed  Europe PubMed DOI
  39. Gronauer,T.F., Mandl,M.M., Lakemeyer,M., Hackl,M.W., Messner,M., Korotkov,V.S., Pachmayr,J. and Sieber,S.A.
    Design and synthesis of tailored human caseinolytic protease P inhibitors
    Chem Commun (Camb)54, 9833-9836. PubMed  Europe PubMed DOI  I
  40. Stahl,M., Korotkov,V.S., Balogh,D., Kick,L.M., Gersch,M., Pahl,A., Kielkowski,P., Richter,K., Schneider,S. and Sieber,S.A.
    Selective activation of human caseinolytic protease P (ClpP)
    Angew Chem Int Ed Engl57, 14602-14607. PubMed  Europe PubMed DOI
    41. 2016
  41. Gersch,M., Stahl,M., Poreba,M., Dahmen,M., Dziedzic,A., Drag,M. and Sieber,S.A.
    Barrel-shaped ClpP proteases display attenuated cleavage specificities
    ACS Chem Biol11, 389-399. PubMed  Europe PubMed DOI  P
  42. Pryde,K.R., Taanman,J.W. and Schapira,A.H.
    A LON-ClpP proteolytic axis degrades complex I to extinguish ROS production in depolarized mitochondria
    Cell Rep17, 2522-2531. PubMed  Europe PubMed DOI
    43. 2015
  43. Cole,A., Wang,Z., Coyaud,E., Voisin,V., Gronda,M., Jitkova,Y., Mattson,R., Hurren,R., Babovic,S., Maclean,N., Restall,I., Wang,X., Jeyaraju,D.V., Sukhai,M.A., Prabha,S., Bashir,S., Ramakrishnan,A., Leung,E., Qia,Y.H., Zhang,N., Combes,K.R., Ketela,T., Lin,F., Houry,W.A., Aman,A., Al-Awar,R., Zheng,W., Wienholds,E., Xu,C.J., Dick,J., Wang,J.C., Moffat,J., Minden,M.D., Eaves,C.J., Bader,G.D., Hao,Z., Kornblau,S.M., Raught,B. and Schimmer,A.D.
    Inhibition of the mitochondrial protease ClpP as a therapeutic strategy for human acute myeloid leukemia
    Cancer Cell27, 864-876. PubMed  Europe PubMed DOI  K
    44. 2013
  44. Jenkinson,E.M., Rehman,A.U., Walsh,T., Clayton-Smith,J., Lee,K., Morell,R.J., Drummond,M.C., Khan,S.N., Naeem,M.A., Rauf,B., Billington,N., Schultz,J.M., Urquhart,J.E., Lee,M.K., Berry,A., Hanley,N.A., Mehta,S., Cilliers,D., Clayton,P.E., Kingston,H., Smith,M.J., Warner,T.T., Black,G.C., Trump,D., Davis,J.R., Ahmad,W., Leal,S.M., Riazuddin,S., King,M.C., Friedman,T.B. and Newman,W.G.
    Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease
    Am J Hum Genet92, 605-613. PubMed  Europe PubMed DOI  M
    45. 2005
  45. [YEAR:22-8-2005]Kang,S.G., Dimitrova,M.N., Ortega,J., Ginsburg,A. and Maurizi,M.R.
    Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX
    J Biol Chem280, 35424-35432. PubMed  Europe PubMed DOI
    46. 2004
  46. Kang,S.G., Maurizi,M.R., Thompson,M., Mueser,T. and Ahvazi,B.
    Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP
    J Struct Biol148, 338-352. PubMed  Europe PubMed DOI  S
    47. 2002
  47. [YEAR:7-6-2002]Kang,S.G., Ortega,J., Singh,S.K., Wang,N., Huang,N.N., Steven,A.C. and Maurizi,M.R.
    Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP
    J Biol Chem277, 21095-21102. PubMed  Europe PubMed DOI
    48. 2000
  48. Andresen,B.S., Corydon,T.J., Wilsbech,M., Bross,P., Schroeder,L.D., Hindkjaer,T.F., Bolund,L. and Gregersen,N.
    Characterization of mouse Clpp protease cDNA, gene, and protein
    Mamm Genome11, 275-280. PubMed  Europe PubMed DOI
  49. Corydon,T.J., Wilsbech,M., Jespersgaard,C., Andresen,B.S., Borglum,A.D., Pedersen,S., Bolund,L., Gregersen,N. and Bross,P.
    Human and mouse mitochondrial orthologs of bacterial ClpX
    Mamm Genome11, 899-905. PubMed  Europe PubMed
    50. 1999
  50. [YEAR:1-10-1999]de Sagarra,M.R., Mayo,I., Marco,S., Rodriguez-Vilarino,S., Oliva,J., Carrascosa,J.L. and Casta n,J.G.
    Mitochondrial localization and oligomeric structure of HClpP, the human homologue of E. coli ClpP
    J Mol Biol292, 819-825. PubMed  Europe PubMed DOI
  51. [YEAR:4-6-1999]Santagata,S., Bhattacharyya,D., Wang,F.H., Singha,N., Hodtsev,A. and Spanopoulou,E.
    Molecular cloning and characterization of a mouse homolog of bacterial ClpX, a novel mammalian class II member of the Hsp100/Clp chaperone family
    J Biol Chem274, 16311-16319. PubMed  Europe PubMed DOI
    52. 1998
  52. [YEAR:1-4-1998]Corydon,T.J., Bross,P., Holst,H.U., Neve,S., Kristiansen,K., Gregersen,N. and Bolund,L.
    A human homologue of Escherichia coli ClpP caseinolytic protease: recombinant expression, intracellular processing and subcellular localization
    Biochem J331, 309-316. PubMed  Europe PubMed
    53. 1995
  53. Bross,P., Andresen,B.S., Knudsen,I., Kruse,T.A. and Gregersen,N.
    Human ClpP protease: CDNA sequence, tissue-specific expression and chromosomal assignment of the gene
    FEBS Lett377, 249-252. PubMed  Europe PubMed DOI

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