Htra2

Summary

Gene Symbol: Htra2
Description: HtrA serine peptidase 2
Alias: AI481710, Omi, Prss25, mnd2, serine protease HTRA2, mitochondrial, high temperature requirement protein A2, motor neuron degeneration 2, omi stress-regulated endoprotease, protease, serine, 25, serine protease 25, serine protease OMI, serine proteinase OMI
Species: mouse
Products:     Htra2

Top Publications

  1. Li B, Hu Q, Wang H, Man N, Ren H, Wen L, et al. Omi/HtrA2 is a positive regulator of autophagy that facilitates the degradation of mutant proteins involved in neurodegenerative diseases. Cell Death Differ. 2010;17:1773-84 pubmed publisher
    ..Loss of its protease activity in mnd2 (motor neuron degeneration 2) mice is associated with neurodegeneration...
  2. Kang S, Louboutin J, Datta P, Landel C, Martinez D, Zervos A, et al. Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature aging. Cell Death Differ. 2013;20:259-69 pubmed publisher
    ..30-40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2/Omi...
  3. Kieper N, Holmström K, Ciceri D, Fiesel F, Wolburg H, Ziviani E, et al. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1. Exp Cell Res. 2010;316:1213-24 pubmed publisher
    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease...
  4. Strauss K, Martins L, Plun Favreau H, Marx F, Kautzmann S, Berg D, et al. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet. 2005;14:2099-111 pubmed
    Recently targeted disruption of Omi/HtrA2 has been found to cause neurodegeneration and a parkinsonian phenotype in mice...
  5. Martins L, Morrison A, Klupsch K, Fedele V, Moisoi N, Teismann P, et al. Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol Cell Biol. 2004;24:9848-62 pubmed
    ..report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary ..
  6. Goo H, Jung M, Han S, Rhim H, Kang S. HtrA2/Omi deficiency causes damage and mutation of mitochondrial DNA. Biochim Biophys Acta. 2013;1833:1866-75 pubmed publisher
    High-temperature requirement protein A2 (HtrA2), a serine protease, localizes in the mitochondria and has diverse roles, including maintenance of mitochondrial homeostasis and regulation of cellular apoptosis...
  7. Martins L, Iaccarino I, Tenev T, Gschmeissner S, Totty N, Lemoine N, et al. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem. 2002;277:439-44 pubmed
    ..Here we have identified the serine protease Omi/HtrA2 as a second mammalian XIAP-binding protein with a Reaper-like motif...
  8. Verhagen A, Silke J, Ekert P, Pakusch M, Kaufmann H, Connolly L, et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem. 2002;277:445-54 pubmed
    ..We now demonstrate that HtrA2, a mammalian homologue of the Escherichia coli heat shock-inducible protein HtrA, can bind to MIHA/XIAP, MIHB, and ..
  9. Jones J, Datta P, Srinivasula S, Ji W, Gupta S, Zhang Z, et al. Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature. 2003;425:721-7 pubmed
    The mouse mutant mnd2 (motor neuron degeneration 2) exhibits muscle wasting, neurodegeneration, involution of the spleen and thymus, and death by 40 days of age...

More Information

Publications64

  1. Jones J, Albin R, Feldman E, Simin K, Schuster T, Dunnick W, et al. mnd2: a new mouse model of inherited motor neuron disease. Genomics. 1993;16:669-77 pubmed
    The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age...
  2. Marabese M, Mazzoletti M, Vikhanskaya F, Broggini M. HtrA2 enhances the apoptotic functions of p73 on bax. Cell Death Differ. 2008;15:849-58 pubmed publisher
    ..for the p73-alpha form that occurs through proteolytic cleavage connected to the activity of the serine protease HtrA2. Following apoptotic stimuli, HtrA2 accumulates in the nucleus and cleaves p73alpha in the C-terminal portion, ..
  3. van Loo G, van Gurp M, Depuydt B, Srinivasula S, Rodriguez I, Alnemri E, et al. The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ. 2002;9:20-6 pubmed
    ..mitochondria exposed to recombinant tBid, a proapoptotic Bcl-2 member, revealed the presence of the serine protease Omi, also called HtrA2. This release was prevented in mitochondria derived from Bcl-2-transgenic mice...
  4. Rathke Hartlieb S, Schlomann U, Heimann P, Meisler M, Jockusch H, Bartsch J. Progressive loss of striatal neurons causes motor dysfunction in MND2 mutant mice and is not prevented by Bcl-2. Exp Neurol. 2002;175:87-97 pubmed
    The mouse mutant "motoneuron disease 2" (MND2, mnd2 on Chr 6) was originally characterized as a spinal muscular atrophy (SMA) because degenerating motoneurons were observed in late stages of the disease...
  5. Fitzgerald J, Camprubi M, Dunn L, Wu H, Ip N, Kruger R, et al. Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function. Cell Death Differ. 2012;19:257-66 pubmed publisher
    The role of the serine protease HtrA2 in neuroprotection was initially identified by the demonstration of neurodegeneration in mice lacking HtrA2 expression or function, and the interesting finding that mutations adjacent to two putative ..
  6. Moisoi N, Klupsch K, Fedele V, East P, Sharma S, Renton A, et al. Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response. Cell Death Differ. 2009;16:449-64 pubmed publisher
    ..Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans...
  7. Inagaki R, Tagawa K, Qi M, Enokido Y, Ito H, Tamura T, et al. Omi / HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington's disease. Eur J Neurosci. 2008;28:30-40 pubmed publisher
    ..We here report that Omi/HtrA2, a mitochondrial protein regulating survival and apoptosis of cells, decreases selectively in striatal neurons ..
  8. Plun Favreau H, Burchell V, Holmström K, Yao Z, Deas E, Cain K, et al. HtrA2 deficiency causes mitochondrial uncoupling through the F₁F₀-ATP synthase and consequent ATP depletion. Cell Death Dis. 2012;3:e335 pubmed publisher
    Loss of the mitochondrial protease HtrA2 (Omi) in mice leads to mitochondrial dysfunction, neurodegeneration and premature death, but the mechanism underlying this pathology remains unclear...
  9. Ideguchi K, Shimizu S, Okumura M, Tsujimoto Y. Cyclophilin D-dependent mitochondrial permeability transition is not involved in neurodegeneration in mnd2 mutant mice. Biochem Biophys Res Commun. 2010;393:264-7 pubmed publisher
    Parkinson's disease (PD) is a common neurodegenerative disorder. The motor neuron degeneration 2 mutant (mnd2) mouse exhibits loss of striatal neurons, muscle wasting, weight loss, and death within 40days of birth, and is considered to ..
  10. Gray C, Ward R, Karran E, Turconi S, Rowles A, Viglienghi D, et al. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur J Biochem. 2000;267:5699-710 pubmed
    Human HtrA2 is a novel member of the HtrA serine protease family and shows extensive homology to the Escherichia coli HtrA genes that are essential for bacterial survival at high temperatures...
  11. Liu Z, Li H, Derouet M, Berezkin A, Sasazuki T, Shirasawa S, et al. Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm. J Biol Chem. 2006;281:14738-47 pubmed
    ..Instead, anoikis of intestinal epithelial cells is triggered by the release of a mitochondrial protein Omi/HtrA2, an event driven by detachment-induced down-regulation of Bcl-X(L)...
  12. Krick S, Shi S, Ju W, Faul C, Tsai S, Mundel P, et al. Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease. Proc Natl Acad Sci U S A. 2008;105:14106-11 pubmed publisher
    Cellular localization determines whether the serine protease HtrA2 exerts pro- or antiapoptotic functions...
  13. Jang W, Weber J, Harkins E, Meisler M. Localization of the rhotekin gene RTKN on the physical maps of mouse chromosome 6 and human chromosome 2p13 and exclusion as a candidate for mnd2 and LGMD2B. Genomics. 1997;40:506-7 pubmed
  14. Rami A, Langhagen A. Specific alterations of the HtrA2/HAX-1 ratio in the penumbra upon focal cerebral ischemia in mice. Neurochem Res. 2012;37:548-56 pubmed publisher
    ..in mice and investigated principally the dynamic changes of HAX-1 expression and other apoptotic agents such as HtrA2, AIF and caspase-3...
  15. Wu J, Li M, Cao L, Sun M, Chen D, Ren H, et al. Protease Omi cleaving Hax-1 protein contributes to OGD/R-induced mitochondrial damage in neuroblastoma N2a cells and cerebral injury in MCAO mice. Acta Pharmacol Sin. 2015;36:1043-52 pubmed publisher
    In the penumbra after focal cerebral ischemia, an increase of protease Omi is linked to a decrease of Hs1-associated protein X-1 (Hax-1), a protein belonging to the Bcl-2 family...
  16. Nunes M, Blanc I, Maes J, Fellous M, Robert B, McElreavey K. NSPc1, a novel mammalian Polycomb gene, is expressed in neural crest-derived structures of the peripheral nervous system. Mech Dev. 2001;102:219-22 pubmed
    ..At 11.5 dpc, transcripts are present in a subset of neural crest cell derivatives of the peripheral nervous system, and in the neural tube. NSPc1 expression is ubiquitous in adult tissue. ..
  17. Encinas J, Kikuchi K, Chedotal A, de Castro F, Goodman C, Kimura T. Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family. Proc Natl Acad Sci U S A. 1999;96:2491-6 pubmed
    ..This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.
  18. Mohamedmohaideen N, Palaninathan S, Morin P, Williams B, Braunstein M, Tichy S, et al. Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry. 2008;47:6092-102 pubmed publisher
    ..Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB...
  19. Patel A, Rochelle J, Jones J, Sumegi J, Uhl G, Seldin M, et al. Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3. Genomics. 1995;25:314-7 pubmed
    ..Analysis of a cross segregating the neurological mutant mnd2 excluded Taut as a candidate gene for this closely linked mutation...
  20. Rathke Hartlieb S, Budde P, Ewert S, Schlomann U, Staege M, Jockusch H, et al. Elevated expression of membrane type 1 metalloproteinase (MT1-MMP) in reactive astrocytes following neurodegeneration in mouse central nervous system. FEBS Lett. 2000;481:227-34 pubmed
    ..In primary astrocyte cultures, MT1-MMP mRNA was upregulated by exogeneous tumor necrosis factor alpha. Increased plasma membrane and secreted MMP activities were found in primary WR astrocytes. ..
  21. Ma Q, Hu Q, Xu R, Zhen X, Wang G. Protease Omi facilitates neurite outgrowth in mouse neuroblastoma N2a cells by cleaving transcription factor E2F1. Acta Pharmacol Sin. 2015;36:966-75 pubmed publisher
    ..Mouse neuroblastoma N2a cells and Omi protease-deficient mnd2 mice were used in this study...
  22. Sosna J, Voigt S, Mathieu S, Kabelitz D, Trad A, Janssen O, et al. The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis. Cell Commun Signal. 2013;11:76 pubmed publisher
    ..A screen for proteins labeled by a fluorescent TPCK derivative in necroptotic cells identified HtrA2/Omi (a serine protease previously implicated in PCD) as a promising candidate...
  23. Jang W, Hua A, Spilson S, Miller W, Roe B, Meisler M. Comparative sequence of human and mouse BAC clones from the mnd2 region of chromosome 2p13. Genome Res. 1999;9:53-61 pubmed
    The mnd2 mutation on mouse chromosome 6 produces a progressive neuromuscular disorder...
  24. Weber J, Jang W, Simin K, Lu W, Yu J, Meisler M. High-resolution genetic, physical, and transcript map of the mnd2 region of mouse chromosome 6. Genomics. 1998;54:107-15 pubmed
    The autosomal recessive mutation mnd2 is responsible for a lethal neuromuscular wasting disorder in the mouse...
  25. Swaroop A, Yang Feng T, Liu W, Gieser L, Barrow L, Chen K, et al. Molecular characterization of a novel human gene, SEC13R, related to the yeast secretory pathway gene SEC13, and mapping to a conserved linkage group on human chromosome 3p24-p25 and mouse chromosome 6. Hum Mol Genet. 1994;3:1281-6 pubmed
    ..The mouse Sec13r gene was mapped to the conserved linkage group on chromosome 6 that corresponds to human chromosome 3p24-p25. ..
  26. Park H, Kim G, Nam M, Seong G, Han C, Chung K, et al. The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity. Biochem Biophys Res Commun. 2009;387:537-42 pubmed publisher
    The serine protease HtrA2 is important in regulating not only apoptosis but also cellular homeostasis...
  27. Barrow L, Simin K, Jones J, Lee D, Meisler M. Conserved linkage of early growth response 4, annexin 4, and transforming growth factor alpha on mouse chromosome 6. Genomics. 1994;19:388-90 pubmed
    ..The genes are located approximately 2 cM distal to mnd2, a mouse mutation causing neuromuscular disease...
  28. Kim J, Kim D, Park M, Cho H, Zervos A, Bonventre J, et al. Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced by unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2010;298:F1332-40 pubmed publisher
    ..The results of our recent studies have shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, performs a crucial function in renal tubular epithelial ..
  29. Goo H, Rhim H, Kang S. HtrA2/Omi influences the stability of LON protease 1 and prohibitin, proteins involved in mitochondrial homeostasis. Exp Cell Res. 2014;328:456-65 pubmed publisher
    ..effect of the HtrA2 protease on the stability of the above mitochondrial quality control proteins in motor neuron degeneration 2 (mnd2) mice, which have a greatly reduced protease activity as a result of a Ser276Cys missense ..
  30. Saito A, Hayashi T, Okuno S, Nishi T, Chan P. Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1. Brain Res Mol Brain Res. 2004;127:89-95 pubmed
    Omi/HtrA2 is a novel protein that contributes to the regulation of mitochondrial apoptosis after a variety of cell death stimuli in vitro and is thought to negatively control the inhibitor-of-apoptosis protein (IAP) family...
  31. Ulett G, Maclean K, Nekkalapu S, Cleveland J, Adderson E. Mechanisms of group B streptococcal-induced apoptosis of murine macrophages. J Immunol. 2005;175:2555-62 pubmed
    ..GBS induces unique changes in the regulation and localization of the apoptotic regulators Bad, 14-3-3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome c and the activation of caspase-9 and ..
  32. Liu H, Gao E, Hu A, Tao L, Qu Y, Most P, et al. Role of Omi/HtrA2 in apoptotic cell death after myocardial ischemia and reperfusion. Circulation. 2005;111:90-6 pubmed
    Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent as well as caspase-independent cell death...
  33. Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber S, et al. Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. J Biol Chem. 2004;279:24813-25 pubmed
    ..Thus Tim50 is important for both mitochondrial function and early neuronal development. ..
  34. Ding X, Patel M, Shen D, Herzlich A, Cao X, Villasmil R, et al. Enhanced HtrA2/Omi expression in oxidative injury to retinal pigment epithelial cells and murine models of neurodegeneration. Invest Ophthalmol Vis Sci. 2009;50:4957-66 pubmed publisher
    To investigate the role of HtrA2/Omi, a nuclear-encoded mitochondrial serine protease with a proapoptosis function, under H(2)O(2)-induced oxidative stress in human RPE, in the Ccl2(-)(/)(-)Cx3cr1(-)(/)(-) double-knockout (DKO) mouse ..
  35. Casadei N, Sood P, Ulrich T, Fallier Becker P, Kieper N, Helling S, et al. Mitochondrial defects and neurodegeneration in mice overexpressing wild-type or G399S mutant HtrA2. Hum Mol Genet. 2016;25:459-71 pubmed publisher
    The protease HtrA2 has a protective role inside mitochondria, but promotes apoptosis under stress. We previously identified the G399S HtrA2 mutation in Parkinson's disease (PD) patients and reported mitochondrial dysfunction in vitro...
  36. Jang W, Weber J, Tokito M, Holzbaur E, Meisler M. Mouse p150Glued (dynactin 1) cDNA sequence and evaluation as a candidate for the neuromuscular disease mutation mnd2. Biochem Biophys Res Commun. 1997;231:344-7 pubmed
    ..gene was previously mapped in the central region of mouse chromosome 6, close to the neuromuscular disease gene mnd2. Northern blot analysis, complete sequencing of the cDNA, Western blot, and functional tests of the protein did not ..
  37. Xu R, Hu Q, Ma Q, Liu C, Wang G. The protease Omi regulates mitochondrial biogenesis through the GSK3β/PGC-1α pathway. Cell Death Dis. 2014;5:e1373 pubmed publisher
    ..mitochondrial dysfunction, neurodegeneration with parkinsonian features and premature death in mnd2 (motor neuron degeneration 2) mice. However, the detailed mechanisms underlying this pathology remain largely unknown...
  38. Yoshida T, Mizuta T, Shimizu S. Neurodegeneration in mnd2 mutant mice is not prevented by parkin transgene. Biochem Biophys Res Commun. 2010;402:676-9 pubmed publisher
    Parkinson's disease (PD) is a common neurodegenerative disorder. The motor neuron degeneration 2 mutant (mnd2) mouse is considered to be an animal model of PD, and exhibits striatal neuron loss, severe muscle wasting, weight loss and ..
  39. Andree M, Seeger J, Schüll S, Coutelle O, Wagner Stippich D, Wiegmann K, et al. BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella. EMBO J. 2014;33:2171-87 pubmed publisher
    ..Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization. ..
  40. Liu X, Lei J, Wang K, Ma L, Liu D, Du Y, et al. Mitochondrial Omi/HtrA2 Promotes Caspase Activation Through Cleavage of HAX-1 in Aging Heart. Rejuvenation Res. 2017;20:183-192 pubmed publisher
    ..Omi/HtrA2, a serine protease, locates in mitochondria and involves in mitochondrial homeostasis...
  41. Chao J, Parganas E, Boyd K, Hong C, Opferman J, Ihle J. Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons. Nature. 2008;452:98-102 pubmed publisher
    ..requires the interaction of Hax1 with the mitochondrial proteases Parl (presenilin-associated, rhomboid-like) and HtrA2 (high-temperature-regulated A2, also known as Omi)...
  42. Maus F, Sakry D, Binamé F, Karram K, Rajalingam K, Watts C, et al. The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2. PLoS ONE. 2015;10:e0137311 pubmed publisher
    ..Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to ..
  43. Behbahani H, Pavlov P, Wiehager B, Nishimura T, Winblad B, Ankarcrona M. Association of Omi/HtrA2 with ?-secretase in mitochondria. Neurochem Int. 2010;57:668-75 pubmed publisher
    Omi/HtrA2, a mitochondrial serine protease with chaperone activity, is involved in varied intracellular processes. Dysfunctional Omi/HtrA2 has thus been implicated in various neurodegenerative disorders...
  44. Zhang F, Yu T, Yi C, Sun X. Radiation-inducible HtrA2 gene enhances radiosensitivity of uveal melanoma OCM-1 cells in vitro and in vivo. Clin Exp Ophthalmol. 2014;42:761-8 pubmed publisher
    ..an effective approach for the treatment of patients with uveal melanomas, we designed a strategy that combines HtrA2 gene therapy and radiation therapy...
  45. Yang Q, Church Hajduk R, Ren J, Newton M, Du C. Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. Genes Dev. 2003;17:1487-96 pubmed
    Omi/HtrA2 is a mitochondrial serine protease that is released into the cytosol during apoptosis to antagonize inhibitors of apoptosis (IAPs) and contribute to caspase-independent cell death...
  46. Wang K, Zhang J, Liu J, Tian J, Wu Y, Wang X, et al. Variations in the protein level of Omi/HtrA2 in the heart of aged rats may contribute to the increased susceptibility of cardiomyocytes to ischemia/reperfusion injury and cell death : Omi/HtrA2 and aged heart injury. Age (Dordr). 2013;35:733-46 pubmed publisher
    ..XIAP was balanced by two mitochondria proteins, Omi/HtrA2 and Smac/DIABLO...
  47. Cilenti L, Ambivero C, Ward N, Alnemri E, Germain D, Zervos A. Inactivation of Omi/HtrA2 protease leads to the deregulation of mitochondrial Mulan E3 ubiquitin ligase and increased mitophagy. Biochim Biophys Acta. 2014;1843:1295-307 pubmed publisher
    ..Loss of Omi/HtrA2's protease activity causes the neuromuscular disorder of the mnd2 (motor neuron degeneration 2) mutant mice...
  48. Hu Q, Li B, Xu R, Chen D, Mu C, Fei E, et al. The protease Omi cleaves the mitogen-activated protein kinase kinase MEK1 to inhibit microglial activation. Sci Signal. 2012;5:ra61 pubmed publisher
    ..The severe neurodegeneration and neuroinflammation that occur in mnd2 (motor neuron degeneration 2) mice result from loss of the protease activity of Omi by the point mutation S276C; however, the ..
  49. Liu M, Liu M, Shen Y, Kim J, Lee B, Lee Y, et al. Transgenic mice with neuron-specific overexpression of HtrA2/Omi suggest a neuroprotective role for HtrA2/Omi. Biochem Biophys Res Commun. 2007;362:295-300 pubmed
    Mammalian serine protease HtrA2/Omi has been known as an apoptosis inducer involved inactivation of caspase-dependent as well as caspase-independent cell death...
  50. Kim J, Kim S, Kim B, Lee H, Kim I, Yun J, et al. Identification of a novel anti-apoptotic E3 ubiquitin ligase that ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2, and ARTS. J Biol Chem. 2013;288:12014-21 pubmed publisher
    ..AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. However, AREL1 was cytosolic and did not localize to nuclei or mitochondria...
  51. Dannenberg J, Schuijff L, Dekker M, van der Valk M, te Riele H. Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130. Genes Dev. 2004;18:2952-62 pubmed
    ..The redundancy of the retinoblastoma proteins in vivo is reflected by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro. ..
  52. Yamauchi S, Hou Y, Guo A, Hirata H, Nakajima W, Yip A, et al. p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion. J Cell Biol. 2014;204:1191-207 pubmed publisher
    ..Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton...
  53. Bishop M, Chakraborty S, Matthews G, Dougalis A, Wood N, Festenstein R, et al. Hyperexcitable substantia nigra dopamine neurons in PINK1- and HtrA2/Omi-deficient mice. J Neurophysiol. 2010;104:3009-20 pubmed publisher
    ..Here we show that deletion of PD-associated genes, PINK1 or HtrA2/Omi, leads to a functional reduction in the activity of small-conductance Ca(2+)-activated potassium channels...
  54. Patterson V, Zullo A, Koenig C, Stoessel S, Jo H, Liu X, et al. Neural-specific deletion of Htra2 causes cerebellar neurodegeneration and defective processing of mitochondrial OPA1. PLoS ONE. 2014;9:e115789 pubmed publisher
    b>HTRA2, a serine protease in the intermembrane space, has important functions in mitochondrial stress signaling while its abnormal activity may contribute to the development of Parkinson's disease...
  55. Yoshioka H, Katsu M, Sakata H, Okami N, Wakai T, Kinouchi H, et al. The role of PARL and HtrA2 in striatal neuronal injury after transient global cerebral ischemia. J Cereb Blood Flow Metab. 2013;33:1658-65 pubmed publisher
    The presenilin-associated rhomboid-like (PARL) protein and high temperature requirement factor A2 (HtrA2) are key regulators of mitochondrial integrity and play pivotal roles in apoptosis...