The Rhomboid-Like Superfamily: Molecular Mechanisms and Biological Roles

Literature Cited

1. Abba MC, Lacunza E, Nunez MI, Colussi A, Isla-Larrain M. et al. 2009. Rhomboid domain containing 2 (RHBDD2): a novel cancer-related gene over-expressed in breast cancer. Biochim. Biophys. Acta 1792:988–97 [Google Scholar]
2. Adrain C, Freeman M. 2012. New lives for old: evolution of pseudoenzyme function illustrated by iRhoms. Nat. Rev. Mol. Cell Biol. 13:489–98 [Google Scholar]
3. Adrain C, Strisovsky K, Zettl M, Hu L, Lemberg MK, Freeman M. 2011. Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep. 12:421–27 [Google Scholar]
4. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M. 2012. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 335:225–28 [Google Scholar]
5. Ahmedli NB, Gribanova Y, Njoku CC, Naidu A, Young A. et al. 2013. Dynamics of the rhomboid-like RHBDD2 expression in mouse retina and involvement of its human ortholog in retinitis pigmentosa. J. Biol. Chem. 288:9742–54 [Google Scholar]
6. Akiyama Y, Maegawa S. 2007. Sequence features of substrates required for cleavage by GlpG, an Escherichia coli rhomboid protease. Mol. Microbiol. 64:1028–37 [Google Scholar]
7. Bahar A, Simpson DJ, Cutty SJ, Bicknell JE, Hoban PR. et al. 2004. Isolation and characterization of a novel pituitary tumor apoptosis gene. Mol. Endocrinol. 18:1827–39 [Google Scholar]
8. Baker RP, Urban S. 2012. Architectural and thermodynamic principles underlying intramembrane protease function. Nat. Chem. Biol. 8:759–68 [Google Scholar]
9. Baker RP, Wijetilaka R, Urban S. 2006. Two plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLOS Pathog. 2:e113 [Google Scholar]
10. Baker RP, Young K, Feng L, Shi Y, Urban S. 2007. Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc. Natl. Acad. Sci. USA 104:8257–62 [Google Scholar]
11. Baxt LA, Baker RP, Singh U, Urban S. 2008. An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion. Genes Dev. 22:1636–46 [Google Scholar]
12. Baxt LA, Rastew E, Bracha R, Mirelman D, Singh U. 2010. Downregulation of an Entamoeba histolytica rhomboid protease reveals roles in regulating parasite adhesion and phagocytosis. Eukaryot. Cell 9:1283–93 [Google Scholar]
13. Ben-Shem A, Fass D, Bibi E. 2007. Structural basis for intramembrane proteolysis by rhomboid serine proteases. Proc. Natl. Acad. Sci. USA 104:462–66 [Google Scholar]
14. Bier E, Jan LY, Jan YN. 1990. Rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev. 4:190–203 [Google Scholar]
15. Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ. et al. 2012. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am. J. Hum. Genet. 90:340–46 [Google Scholar]
16. Brooks CL, Lazareno-Saez C, Lamoureux JS, Mak MW, Lemieux MJ. 2011. Insights into substrate gating in H. influenzae rhomboid. J. Mol. Biol. 407:687–97 [Google Scholar]
17. Brooks CL, Lemieux MJ. 2013. Untangling structure-function relationships in the rhomboid family of intramembrane proteases. Biochim. Biophys. Acta 1828:2862–72 [Google Scholar]
18. Brossier F, Jewett TJ, Sibley LD, Urban S. 2005. A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by toxoplasma. Proc. Natl. Acad. Sci. USA 102:4146–51 [Google Scholar]
19. Canzoneri R, Lacunza E, Isla Larrain M, Croce MV, Abba MC. 2013. Rhomboid family gene expression profiling in breast normal tissue and tumor samples. Tumor Biol. 35:1451–58 [Google Scholar]
20. Carruthers VB, Blackman MJ. 2005. A new release on life: emerging concepts in proteolysis and parasite invasion. Mol. Microbiol. 55:1617–30 [Google Scholar]
21. Chan EY, McQuibban GA. 2013. The mitochondrial rhomboid protease: its rise from obscurity to the pinnacle of disease-relevant genes. Biochim. Biophys. Acta 1828:2916–25 [Google Scholar]
22. Chanthaphavong RS, Loughran PA, Lee TY, Scott MJ, Billiar TR. 2012. A role for cGMP in inducible nitric-oxide synthase (iNOS)-induced tumor necrosis factor (TNF) α-converting enzyme (TACE/ADAM17) activation, translocation, and TNF receptor 1 (TNFR1) shedding in hepatocytes. J. Biol. Chem. 287:35887–98 [Google Scholar]
23. Christianson JC, Olzmann JA, Shaler TA, Sowa ME, Bennett EJ. et al. 2011. Defining human ERAD networks through an integrative mapping strategy. Nat. Cell Biol. 14:93–105 [Google Scholar]
24. Christova Y, Adrain C, Bambrough P, Ibrahim A, Freeman M. 2013. Mammalian iRhoms have distinct physiological functions including an essential role in TACE regulation. EMBO Rep. 14:884–90 [Google Scholar]
25. Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L. et al. 2006. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA 1-dependent cristae remodeling. Cell 126:163–75 [Google Scholar]
26. Civitarese AE, MacLean PS, Carling S, Kerr-Bayles L, McMillan RP. et al. 2010. Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL. Cell Metab. 11:412–26 [Google Scholar]
27. Clemmer KM, Sturgill GM, Veenstra A, Rather PN. 2006. Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii. J. Bacteriol. 188:3415–19 [Google Scholar]
28. Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S. et al. 2011. PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum. Mol. Genet. 20:867–79 [Google Scholar]
29. Dickey S, Baker R, Cho S, Urban S. 2013. Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity. Cell 155:1270–81 [Google Scholar]
30. Dowse TJ, Pascall JC, Brown KD, Soldati D. 2005. Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int. J. Parasitol. 35:747–56 [Google Scholar]
31. Duvezin-Caubet S, Koppen M, Wagener J, Zick M, Israel L. et al. 2007. OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria. Mol. Biol. Cell 18:3582–90 [Google Scholar]
32. Esler WP, Kimberly WT, Ostaszewski BL, Diehl TS, Moore CL. et al. 2000. Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1. Nat. Cell Biol. 2:428–34 [Google Scholar]
33. Esser K, Tursun B, Ingenhoven M, Michaelis G, Pratje E. 2002. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1. J. Mol. Biol. 323:835–43 [Google Scholar]
34. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY. et al. 2014. Pfam: the protein families database. Nucleic Acids Res. 42:D222–30 [Google Scholar]
35. Fleig L, Bergbold N, Sahasrabudhe P, Geiger B, Kaltak L, Lemberg MK. 2012. Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins. Mol. Cell 47:558–69 [Google Scholar]
36. Fukino K, Iido A, Teramoto A, Sakamoto G, Kasumi F. et al. 1999. Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers. Genes Chromosom. Cancer 24:345–50 [Google Scholar]
37. Gomes LC, Scorrano L. 2013. Mitochondrial morphology in mitophagy and macroautophagy. Biochim. Biophys. Acta 1833:205–12 [Google Scholar]
38. Greenblatt EJ, Olzmann JA, Kopito RR. 2011. Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum. Nat. Struct. Mol. Biol. 18:1147–52 [Google Scholar]
39. Guichard A, Biehs B, Sturtevant MA, Wickline L, Chacko J. et al. 1999. rhomboid and Star interact synergistically to promote EGFR/MAPK signaling during Drosophila wing vein development. Development 126:2663–76 [Google Scholar]
40. Guillery O, Malka F, Landes T, Guillou E, Blackstone C. et al. 2008. Metalloprotease-mediated opa1 processing is modulated by the mitochondrial membrane potential. Biol. Cell 100:315–25 [Google Scholar]
41. Ha Y, Akiyama Y, Xue Y. 2013. Structure and mechanism of rhomboid protease. J. Biol. Chem. 288:15430–36 [Google Scholar]
42. Hampton RY, Sommer T. 2012. Finding the will and the way of ERAD substrate retrotranslocation. Curr. Opin. Cell Biol. 24:460–66 [Google Scholar]
43. Hatunic M, Stapleton M, Hand E, DeLong C, Crowley VE, Nolan JJ. 2009. The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population. Diabetes Res. Clin. Pract. 83:316–19 [Google Scholar]
44. Heinitz S, Klein C, Djarmati A. 2011. The p.s77n presenilin-associated rhomboid-like protein mutation is not a frequent cause of early-onset Parkinson's disease. Mov. Disord. 26:2441–42 [Google Scholar]
45. Herlan M, Bornhövd C, Hell K, Neupert W, Reichert AS. 2004. Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor. J. Cell Biol. 165:167–73 [Google Scholar]
46. Howell SA, Hackett F, Jongco AM, Withers-Martinez C, Kim K. et al. 2005. Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens. Mol. Microbiol. 57:1342–56 [Google Scholar]
47. Imai Y, Lu B. 2011. Mitochondrial dynamics and mitophagy in Parkinson's disease: Disordered cellular power plant becomes a big deal in a major movement disorder. Curr. Opin. Neurobiol. 21:935–41 [Google Scholar]
48. Issuree PD, Maretzky T, McIlwain DR, Monette S, Qing X. et al. 2013. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. J. Clin. Investig. 123:928–32 [Google Scholar]
49. Ivanova AV, Vortmeyer A, Ivanov SV, Nickerson ML, Maher ER, Lerman MI. 2008. Loss of PL6 protein expression in renal clear cell carcinomas and other VHL-deficient tumours. J. Pathol. 214:46–57 [Google Scholar]
50. Iwaya T, Maesawa C, Ogasawara S, Tamura G. 1998. Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer. Gastroenterology 114:1206–10 [Google Scholar]
51. Jeyaraju DV, Xu L, Letellier MC, Bandaru S, Zunino R. et al. 2006. Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology. Proc. Natl. Acad. Sci. USA 103:18562–67 [Google Scholar]
52. Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. 2010. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 191:933–42 [Google Scholar]
53. Kelsell DP, Risk JM, Leigh IM, Stevens HP, Ellis A. et al. 1996. Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC). Hum. Mol. Genet. 5:857–60 [Google Scholar]
54. Kim YM, Brinkmann MM, Paquet ME, Ploegh HL. 2008. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 452:234–38 [Google Scholar]
55. Kinch LN, Grishin NV. 2013. Bioinformatics perspective on rhomboid intramembrane protease evolution and function. Biochim. Biophys. Acta 1828:2937–43 [Google Scholar]
56. Knop M, Finger A, Braun T, Hellmuth K, Wolf DH. 1996. Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. EMBO J. 15:753–63 [Google Scholar]
57. Knopf RR, Adam Z. 2012. Rhomboid proteases in plants—Still in square one?. Physiol. Plant 145:41–51 [Google Scholar]
58. Knopf RR, Feder A, Mayer K, Lin A, Rozenberg M. et al. 2012. Rhomboid proteins in the chloroplast envelope affect the level of allene oxide synthase in Arabidopsis thaliana. Plant J. 72:559–71 [Google Scholar]
59. Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, Pellegrini L. 2003. The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol. 4:R19 [Google Scholar]
60. Lacunza E, Canzoneri R, Rabassa ME, Zwenger A, Segal-Eiras A. et al. 2012. RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of colorectal cancer. Tumor Biol. 33:2393–99 [Google Scholar]
61. Lacunza E, Rabassa ME, Canzoneri R, Pellon-Maison M, Croce MV. et al. 2013. Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response. Cell Stress Chaperones 19:379–88 [Google Scholar]
62. Lee BL, Moon JE, Shu JH, Yuan L, Newman ZR. et al. 2013. UNC93B1 mediates differential trafficking of endosomal TLRs. eLife 2:e00291 [Google Scholar]
63. Lee JR, Urban S, Garvey CF, Freeman M. 2001. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell 107:161–71 [Google Scholar]
64. Lemberg MK. 2013. Sampling the membrane: function of rhomboid-family proteins. Trends Cell Biol. 23:210–17 [Google Scholar]
65. Lemberg MK, Freeman M. 2007. Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases. Genome Res. 17:1634–46 [Google Scholar]
66. Lemberg MK, Menendez J, Misik A, Garcia M, Koth CM, Freeman M. 2005. Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases. EMBO J. 24:464–72 [Google Scholar]
67. Lemieux MJ, Fischer SJ, Cherney MM, Bateman KS, James MN. 2007. The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. Proc. Natl. Acad. Sci. USA 104:750–54 [Google Scholar]
68. Liao HJ, Carpenter G. 2012. Regulated intramembrane cleavage of the EGF receptor. Traffic 13:1106–12 [Google Scholar]
69. Lilley BN, Ploegh HL. 2004. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429:834–40 [Google Scholar]
70. Lin JW, Meireles P, Prudêncio M, Engelmann S, Annoura T. et al. 2013. Loss-of-function analyses defines vital and redundant functions of the Plasmodium rhomboid protease family. Mol. Microbiol. 88:318–38 [Google Scholar]
71. Liu J, Han C, Xie B, Wu Y, Liu S. et al. 2014. Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO. Nat. Immunol. 15:7612–22 [Google Scholar]
72. Liu J, Liu S, Xia M, Xu S, Wang C. et al. 2013. Rhomboid domain-containing protein 3 is a negative regulator of TLR3-triggered natural killer cell activation. Proc. Natl. Acad. Sci. USA 110:7814–19 [Google Scholar]
73. Lohi O, Urban S, Freeman M. 2004. Diverse substrate recognition mechanisms for rhomboids: Thrombomodulin is cleaved by mammalian rhomboids. Curr. Biol. 14:236–41 [Google Scholar]
74. Maegawa S, Ito K, Akiyama Y. 2005. Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane. Biochemistry 44:13543–52 [Google Scholar]
75. Manolaridis I, Kulkarni K, Dodd RB, Ogasawara S, Zhang Z. et al. 2013. Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1. Nature 504:301–5 [Google Scholar]
76. Maretzky T, McIlwain DR, Issuree PD, Li X, Malapeira J. et al. 2013. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding. Proc. Natl. Acad. Sci. USA 110:11433–38 [Google Scholar]
77. Mayer U, Nusslein-Volhard C. 1988. A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev. 2:1496–511 [Google Scholar]
78. McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K. et al. 2012. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science 335:229–32 [Google Scholar]
79. McQuibban GA, Lee JR, Zheng L, Juusola M, Freeman M. 2006. Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. Curr. Biol. 16:982–89 [Google Scholar]
80. McQuibban GA, Saurya S, Freeman M. 2003. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature 423:537–41 [Google Scholar]
81. Mehnert M, Sommer T, Jarosch E. 2014. Der1 promotes movement of misfolded proteins through the endoplasmic reticulum membrane. Nat. Cell Biol. 16:77–86 [Google Scholar]
82. Meissner C, Lorenz H, Weihofen A, Selkoe DJ, Lemberg MK. 2011. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J. Neurochem. 117:856–67 [Google Scholar]
83. Moin SM, Urban S. 2012. Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics. eLife 1:e00173 [Google Scholar]
84. Needham PG, Brodsky JL. 2013. How early studies on secreted and membrane protein quality control gave rise to the ER associated degradation (ERAD) pathway: the early history of ERAD. Biochim. Biophys. Acta 1833:2447–57 [Google Scholar]
85. O'Donnell RA, Hackett F, Howell SA, Treeck M, Struck N. et al. 2006. Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J. Cell Biol. 174:1023–33 [Google Scholar]
86. Oda Y, Okada T, Yoshida H, Kaufman RJ, Nagata K, Mori K. 2006. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J. Cell Biol. 172:383–93 [Google Scholar]
87. Olzmann JA, Richter CM, Kopito RR. 2013. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc. Natl. Acad. Sci. USA 110:1345–50 [Google Scholar]
88. Parussini F, Tang Q, Moin SM, Mital J, Urban S, Ward GE. 2012. Intramembrane proteolysis of Toxoplasma apical membrane antigen 1 facilitates host-cell invasion but is dispensable for replication. Proc. Natl. Acad. Sci. USA 109:7463–68 [Google Scholar]
89. Pascall JC, Brown KD. 2004. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2. Biochem. Biophys. Res. Commun. 317:244–52 [Google Scholar]
90. Pierrat OA, Strisovsky K, Christova Y, Large J, Ansell K. et al. 2011. Monocyclic β-lactams are selective, mechanism-based inhibitors of rhomboid intramembrane proteases. ACS Chem. Biol. 6:325–35 [Google Scholar]
91. Pils B, Schultz J. 2004. Inactive enzyme-homologues find new function in regulatory processes. J. Mol. Biol. 340:399–404 [Google Scholar]
92. Presneau N, Dewar K, Forgetta V, Provencher D, Mes-Masson AM, Tonin PN. 2005. Loss of heterozygosity and transcriptome analyses of a 1.2 mb candidate ovarian cancer tumor suppressor locus region at 17q25.1-q25.2. Mol. Carcinog. 43:141–54 [Google Scholar]
93. Rather P. 2013. Role of rhomboid proteases in bacteria. Biochim. Biophys. Acta 1828:2849–54 [Google Scholar]
94. Rawson RB, Zelenski NG, Nijhawan D, Ye J, Sakai J. et al. 1997. Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol. Cell 1:47–57 [Google Scholar]
95. Ren X, Song W, Liu W, Guan X, Miao F. et al. 2013. Rhomboid domain containing 1 inhibits cell apoptosis by upregulating AP-1 activity and its downstream target Bcl-3. FEBS Lett. 587:1793–98 [Google Scholar]
96. Saarinen S, Vahteristo P, Lehtonen R, Aittomäki K, Launonen V. et al. 2012. Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer. Fam. Cancer 11:525–28 [Google Scholar]
97. Saftig P, Reiss K. 2010. The “A disintegrin and metalloproteases” ADAM10 and ADAM17: Novel drug targets with therapeutic potential?. Eur. J. Cell Biol. 90:527–35 [Google Scholar]
98. Santos JM, Ferguson DJP, Blackman MJ, Soldati-Favre D. 2011. Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode. Science 331:473–77 [Google Scholar]
99. Sekine S, Kanamaru Y, Koike M, Nishihara A, Okada M. et al. 2012. Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5. J. Biol. Chem. 287:34635–45 [Google Scholar]
100. Shi G, Lee JR, Grimes DA, Racacho L, Ye D. et al. 2011. Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease. Hum. Mol. Genet. 20:1966–74 [Google Scholar]
101. Sibley LD. 2013. The roles of intramembrane proteases in protozoan parasites. Biochim. Biophys. Acta 1828:2908–15 [Google Scholar]
102. Siggs OM, Xiao N, Wang Y, Shi H, Tomisato W. et al. 2012. iRhom2 is required for the secretion of mouse TNFα. Blood 119:5769–71 [Google Scholar]
103. Sik A, Passer BJ, Koonin EV, Pellegrini L. 2004. Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pβ, a nuclear-targeted peptide. J. Biol. Chem. 279:15323–29 [Google Scholar]
104. Stevenson LG, Strisovsky K, Clemmer KM, Bhatt S, Freeman M, Rather PN. 2007. Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase. Proc. Natl. Acad. Sci. USA 104:1003–8 [Google Scholar]
105. Strisovsky K. 2013. Structural and mechanistic principles of intramembrane proteolysis—lessons from rhomboids. FEBS J. 280:1579–603 [Google Scholar]
106. Strisovsky K, Sharpe HJ, Freeman M. 2009. Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates. Mol. Cell 36:1048–59 [Google Scholar]
107. Tatsuta T, Augustin S, Nolden M, Friedrichs B, Langer T. 2007. m-AAA protease-driven membrane dislocation allows intramembrane cleavage by rhomboid in mitochondria. EMBO J. 26:325–35 [Google Scholar]
108. Thompson EP, Llewellyn Smith SG, Glover BJ. 2012. An Arabidopsis rhomboid protease has roles in the chloroplast and in flower development. J. Exp. Bot. 63:3559–70 [Google Scholar]
109. Todd AE, Orengo CA, Thornton JM. 2002. Sequence and structural differences between enzyme and nonenzyme homologs. Structure 10:1435–51 [Google Scholar]
110. Urban S, Freeman M. 2003. Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol. Cell 11:1425–34 [Google Scholar]
111. Urban S, Lee JR, Freeman M. 2001. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 107:173–82 [Google Scholar]
112. Urban S, Wolfe MS. 2005. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc. Natl. Acad. Sci. USA 102:1883–88 [Google Scholar]
113. Vembar SS, Brodsky JL. 2008. One step at a time: endoplasmic reticulum-associated degradation. Nat. Rev. Mol. Cell Biol. 9:944–57 [Google Scholar]
114. Vera IM, Beatty WL, Sinnis P, Kim K. 2011. Plasmodium protease ROM1 is important for proper formation of the parasitophorous vacuole. PLOS Pathog. 7:e1002197 [Google Scholar]
115. Vinothkumar KR. 2011. Structure of rhomboid protease in a lipid environment. J. Mol. Biol. 407:232–47 [Google Scholar]
116. Vinothkumar KR, Freeman M. 2013. Intramembrane proteolysis by rhomboids: catalytic mechanisms and regulatory principles. Curr. Opin. Struct. Biol. 23:851–58 [Google Scholar]
117. Vinothkumar KR, Pierrat OA, Large JM, Freeman M. 2013. Structure of rhomboid protease in complex with β-lactam inhibitors defines the S2′ cavity. Structure 21:1051–58 [Google Scholar]
118. Vinothkumar KR, Strisovsky K, Andreeva A, Christova Y, Verhelst S, Freeman M. 2010. The structural basis for catalysis and substrate specificity of a rhomboid protease. EMBO J. 29:3797–809 [Google Scholar]
119. Walder K, Kerr-Bayles L, Civitarese A, Jowett J, Curran J. et al. 2005. The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes. Diabetologia 48:459–68 [Google Scholar]
120. Wan C, Fu J, Wang Y, Miao S, Song W, Wang L. 2012. Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid protease RHBDD1-induced proteolysis. PLOS ONE 7:e37452 [Google Scholar]
121. Wang Y, Guan X, Fok KL, Li S, Zhang X. et al. 2008. A novel member of the rhomboid family, RHBDD1, regulates BIK-mediated apoptosis. Cell. Mol. Life Sci. 65:3822–29 [Google Scholar]
122. Wang Y, Song W, Li S, Guan X, Miao S. et al. 2009. Gc-1 mRHBDD1 knockdown spermatogonia cells lose their spermatogenic capacity in mouse seminiferous tubules. BMC Cell Biol. 10:25 [Google Scholar]
123. Wang Y, Zhang Y, Ha Y. 2006. Crystal structure of a rhomboid family intramembrane protease. Nature 444:179–80 [Google Scholar]
124. Wasserman JD, Urban S, Freeman M. 2000. A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signalling. Genes Dev. 14:1651–63 [Google Scholar]
125. Wojnarowicz PM, Provencher DM, Mes-Masson AM, Tonin PN. 2012. Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer. Int. J. Oncol. 40:1865–80 [Google Scholar]
126. Wolf EV, Zeißler A, Vosyka O, Zeiler E, Sieber S, Verhelst SH. 2013. A new class of rhomboid protease inhibitors discovered by activity-based fluorescence polarization. PLOS ONE 8:e72307 [Google Scholar]
127. Wu Z, Yan N, Feng L, Oberstein A, Yan H. et al. 2006. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat. Struct. Mol. Biol. 13:1084–91 [Google Scholar]
128. Xue Y, Chowdhury S, Liu X, Akiyama Y, Ellman J, Ha Y. 2012. Conformational change in rhomboid protease GlpG induced by inhibitor binding to its S′ subsites. Biochemistry 51:3723–31 [Google Scholar]
129. Xue Y, Ha Y. 2011. Catalytic mechanism of rhomboid protease GlpG probed by 3,4-dichloroisocoumarin and diisopropyl fluorophosphonate. J. Biol. Chem. 287:3099–107 [Google Scholar]
130. Xue Y, Ha Y. 2013. Large lateral movement of transmembrane helix S5 is not required for substrate access to the active site of rhomboid intramembrane protease. J. Biol. Chem. 288:16645–54 [Google Scholar]
131. Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA. 2004. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429:841–47 [Google Scholar]
132. Zettl M, Adrain C, Strisovsky K, Lastun V, Freeman M. 2011. Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 145:79–91 [Google Scholar]
133. Zou H, Thomas SM, Yan ZW, Grandis JR, Vogt A, Li LY. 2009. Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells. FASEB J. 23:425–32 [Google Scholar]