intracellular signaling peptides and proteins


Summary: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

Top Publications

  1. Lee Y, Kuo C, Stark J, Shih H, Ann D. HP1 promotes tumor suppressor BRCA1 functions during the DNA damage response. Nucleic Acids Res. 2013;41:5784-98 pubmed publisher
    ..We also suggest that compromising HP1 expression could promote tumorigenesis by impairing the function of the BRCA1 tumor suppressor. ..
  2. Gobbini E, Cesena D, Galbiati A, Lockhart A, Longhese M. Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks. DNA Repair (Amst). 2013;12:791-9 pubmed publisher
    ..Here, we review the early steps of DSB processing and the role of DNA-end structures in activating ATM/Tel1 and ATR/Mec1 in an orderly and reciprocal manner. ..
  3. Nollet M, Leman S. Role of orexin in the pathophysiology of depression: potential for pharmacological intervention. CNS Drugs. 2013;27:411-22 pubmed publisher
  4. Takahashi D, Mori T, Wakabayashi M, Mori Y, Susa K, Zeniya M, et al. KLHL2 interacts with and ubiquitinates WNK kinases. Biochem Biophys Res Commun. 2013;437:457-62 pubmed publisher
    ..These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. ..
  5. Fradet Turcotte A, Canny M, Escribano Diaz C, Orthwein A, Leung C, Huang H, et al. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature. 2013;499:50-4 pubmed publisher
    ..53BP1 is therefore a bivalent histone modification reader that recognizes a histone 'code' produced by DSB signalling. ..
  6. Umlauf D, Bonnet J, Waharte F, Fournier M, Stierlé M, Fischer B, et al. The human TREX-2 complex is stably associated with the nuclear pore basket. J Cell Sci. 2013;126:2656-67 pubmed publisher
    ..Thus, our results show that TREX-2 is an NPC-associated complex in mammalian cells and suggest that it is involved in putative NPC basket-related functions. ..
  7. Fu Q, Chow J, Bernstein K, Makharashvili N, Arora S, Lee C, et al. Phosphorylation-regulated transitions in an oligomeric state control the activity of the Sae2 DNA repair enzyme. Mol Cell Biol. 2014;34:778-93 pubmed publisher
    ..Overall, this analysis provides evidence for a novel type of protein regulation where the activity of an enzyme is controlled dynamically by posttranslational modifications that regulate its solubility and oligomeric state. ..
  8. Kwon Y, Vinayagam A, Sun X, Dephoure N, Gygi S, Hong P, et al. The Hippo signaling pathway interactome. Science. 2013;342:737-40 pubmed publisher
    ..Given the importance of the Hippo pathway in tumor development, the Hippo-PPIN will contribute to our understanding of this network in both normal growth and cancer. ..
  9. Jeong G, Shin S, Seo E, Kwon Y, Heo S, Kim K, et al. TAZ mediates lysophosphatidic acid-induced migration and proliferation of epithelial ovarian cancer cells. Cell Physiol Biochem. 2013;32:253-63 pubmed publisher
    ..In addition, small interfering RNA-mediated silencing of TAZ expression attenuated LPA-stimulated migration of R182 cells. These results suggest that TAZ plays a key role in LPA-stimulated migration of epithelial ovarian cancer cells. ..

More Information


  1. Li M, Zhang S, Wang Z, Zhang B, Wu X, Weng H, et al. Prognostic significance of nemo-like kinase (NLK) expression in patients with gallbladder cancer. Tumour Biol. 2013;34:3995-4000 pubmed publisher
    ..077). In conclusion, overexpression of NLK is closely related to progression of GBC, and NLK could be used as a potential prognostic marker for GBC patients. ..
  2. Thomasy S, Morgan J, Wood J, Murphy C, Russell P. Substratum stiffness and latrunculin B modulate the gene expression of the mechanotransducers YAP and TAZ in human trabecular meshwork cells. Exp Eye Res. 2013;113:66-73 pubmed publisher
    ..Use of these hydrogels may more accurately reflect the alterations occurring in HTM cells in glaucoma after treatment with this drug. ..
  3. Bae D, Jansson P, Huang M, Kovacevic Z, Kalinowski D, Lee C, et al. The role of NDRG1 in the pathology and potential treatment of human cancers. J Clin Pathol. 2013;66:911-7 pubmed publisher
    ..This observation has led to increased interest in the examination of these novel anticancer agents. ..
  4. Scavullo C, Servida F, Lecis D, Onida F, Drago C, Ferrante L, et al. Single-agent Smac-mimetic compounds induce apoptosis in B chronic lymphocytic leukaemia (B-CLL). Leuk Res. 2013;37:809-15 pubmed publisher
    ..In conclusion one of our compounds (Smac66), used as monotherapy and not in combination, is highly active against B-CLL cells thus suggesting a promising therapeutic potential as a new class of antileukemic drugs in haematology. ..
  5. Marcotte D, Zeng W, Hus J, McKenzie A, Hession C, Jin P, et al. Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism. Bioorg Med Chem. 2013;21:4011-9 pubmed publisher
    ..The non-covalent inhibition strategy presents a reasonable course of action to avoid toxic side-effects due to non-specific cysteine modification. ..
  6. Millon Fremillon A, Brunner M, Abed N, Collomb E, Ribba A, Block M, et al. Calcium and calmodulin-dependent serine/threonine protein kinase type II (CaMKII)-mediated intramolecular opening of integrin cytoplasmic domain-associated protein-1 (ICAP-1?) negatively regulates ?1 integrins. J Biol Chem. 2013;288:20248-60 pubmed publisher
    ..Our results point to a molecular mechanism for the phosphorylation-dependent control of ICAP-1? function by CaMKII, allowing the dynamic control of ?1 integrin activation and cell adhesion. ..
  7. Teshiba R, Tajiri T, Sumitomo K, Masumoto K, Taguchi T, Yamamoto K. Identification of a KEAP1 germline mutation in a family with multinodular goitre. PLoS ONE. 2013;8:e65141 pubmed publisher
    ..This study identified the first KEAP1 mutation in MNG. The results provide insights into the pathogenesis of goitre which develops in the organ continuously exposed to oxidative stress during hormone synthesis. ..
  8. Lebold T, Bonaventure P, Shireman B. Selective orexin receptor antagonists. Bioorg Med Chem Lett. 2013;23:4761-9 pubmed publisher
    ..This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. ..
  9. Bassi Z, Audusseau M, Riparbelli M, Callaini G, D Avino P. Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc Natl Acad Sci U S A. 2013;110:9782-7 pubmed publisher
    ..Our findings indicate that CIT-K is likely to act at the top of the midbody-formation hierarchy by connecting and regulating a molecular network of contractile ring components and microtubule-associated proteins...
  10. Singh S, Maeda K, Eid M, Almofty S, Ono M, Pham P, et al. GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy. Nat Commun. 2013;4:1830 pubmed publisher
    ..These findings suggest that GANP-mediated chromatin modification promotes transcription complex recruitment and positioning at immunoglobulin variable loci to favour AID targeting. ..
  11. Carballo J, Panizza S, Serrentino M, Johnson A, Geymonat M, Borde V, et al. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery. PLoS Genet. 2013;9:e1003545 pubmed publisher
    ..Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks. ..
  12. Ziros P, Manolakou S, Habeos I, Lilis I, Chartoumpekis D, Koika V, et al. Nrf2 is commonly activated in papillary thyroid carcinoma, and it controls antioxidant transcriptional responses and viability of cancer cells. J Clin Endocrinol Metab. 2013;98:E1422-7 pubmed publisher
    ..The high activity of Nrf2 in PTC warrants further exploration of this pathway's potential diagnostic, prognostic, and/or therapeutic utility in PTC. ..
  13. Fukutomi T, Takagi K, Mizushima T, Ohuchi N, Yamamoto M. Kinetic, thermodynamic, and structural characterizations of the association between Nrf2-DLGex degron and Keap1. Mol Cell Biol. 2014;34:832-46 pubmed publisher
  14. Orthwein A, Fradet Turcotte A, Noordermeer S, Canny M, Brun C, Strecker J, et al. Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science. 2014;344:189-93 pubmed publisher
    ..We conclude that the capacity of mitotic DSB repair to destabilize the genome explains the necessity for its suppression during mitosis, principally due to the fusogenic potential of mitotic telomeres. ..
  15. Jaumouillé V, Farkash Y, Jaqaman K, Das R, Lowell C, Grinstein S. Actin cytoskeleton reorganization by Syk regulates Fc? receptor responsiveness by increasing its lateral mobility and clustering. Dev Cell. 2014;29:534-546 pubmed publisher
  16. McKenzie C, Bassi Z, Debski J, Gottardo M, Callaini G, Dadlez M, et al. Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis. Open Biol. 2016;6: pubmed publisher
    ..Our results identify, for the first time, a cross-regulatory mechanism between two kinases during cytokinesis, which is crucial for establishing the stereotyped organization of midbody proteins. ..
  17. Wang Z, Liu P, Zhou X, Wang T, Feng X, Sun Y, et al. Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ. Cancer Res. 2017;77:2413-2423 pubmed publisher
    ..Overall, these results indicate a critical role of the YAP/TAZ axis in ETAR signaling. Cancer Res; 77(9); 2413-23. ©2017 AACR. ..
  18. Lindau A, Härdtner C, Hergeth S, Blanz K, Dufner B, Hoppe N, et al. Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression. Basic Res Cardiol. 2016;111:20 pubmed publisher
  19. Middelhoff M, Westphalen C, Hayakawa Y, Yan K, Gershon M, Wang T, et al. Dclk1-expressing tuft cells: critical modulators of the intestinal niche?. Am J Physiol Gastrointest Liver Physiol. 2017;313:G285-G299 pubmed publisher
    ..Hence, we outline and discuss emerging evidence that strongly supports tuft cells as key regulatory cells in the complex network of the intestinal microenvironment. ..
  20. Galateau Salle F, Churg A, Roggli V, Travis W. The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification. J Thorac Oncol. 2016;11:142-54 pubmed publisher
    ..Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express β-catenin by immunohistochemistry. ..
  21. Mao Q, Huang X, He J, Liang W, Peng Y, Su J, et al. A novel method for endothelial cell isolation. Oncol Rep. 2016;35:1652-6 pubmed publisher
    ..The modified method provides CD105+ cells with superior conditions for mechanistic research on the development of vessel-based disease. ..
  22. Kruglova N, Meshkova T, Kopylov A, Mazurov D, Filatov A. Constitutive and activation-dependent phosphorylation of lymphocyte phosphatase-associated phosphoprotein (LPAP). PLoS ONE. 2017;12:e0182468 pubmed publisher
    ..Ser-153 exhibited a high basal level of phosphorylation in both resting and activated cells. Therefore, we suggest that LPAP may function as a co-regulator of T-cell signaling. ..
  23. Kim M, Kim J, Hong H, Lee S, Lee J, Jung E, et al. Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. EMBO J. 2016;35:462-78 pubmed publisher
    ..These results suggest that inhibition of actin remodeling is a potential strategy to suppress resistance in BRAF inhibitor therapies. ..
  24. Lane S, Morgan S, Wu T, Collins J, Merriman J, Elinati E, et al. DNA damage induces a kinetochore-based ATM/ATR-independent SAC arrest unique to the first meiotic division in mouse oocytes. Development. 2017;144:3475-3486 pubmed publisher
    ..Therefore, mouse oocytes have a unique ability to sense DNA damage rapidly by activating the checkpoint at their kinetochores. ..
  25. Hayashi S, Uehara D, Tanimoto K, Mizuno S, Chinen Y, Fukumura S, et al. Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). PLoS ONE. 2017;12:e0181791 pubmed publisher
  26. Algarni M, Stoessl A. The role of biomarkers and imaging in Parkinson's disease. Expert Rev Neurother. 2016;16:187-203 pubmed publisher
  27. Elsarraj H, Valdez K, Hong Y, Grimm S, Ricci L, Fan F, et al. NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer. Cancer Res. 2017;77:3802-3813 pubmed publisher
    ..i>Cancer Res; 77(14); 3802-13. ©2017 AACR. ..
  28. Sarkar S, Popov V, O Connell M, Stevenson H, Lee B, Obeid R, et al. A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially useful for assessing colon cancer risk after screening colonoscopy. Lab Invest. 2017;97:1245-1261 pubmed publisher
    ..We now report that DCLK1-S-specific Ab may help to identify high-risk patients at the time of index/screening colonoscopy. ..
  29. Su T, Ludwig M, Xu J, Fehon R. Kibra and Merlin Activate the Hippo Pathway Spatially Distinct from and Independent of Expanded. Dev Cell. 2017;40:478-490.e3 pubmed publisher
  30. Liu Q, Gao Q, Zhang Y, Li Z, Mei X. MicroRNA-590 promotes pathogenic Th17 cell differentiation through targeting Tob1 and is associated with multiple sclerosis. Biochem Biophys Res Commun. 2017;493:901-908 pubmed publisher
    ..Our finding suggest that miR-590 could enhance pathogenic Th17 differentiation in MS and augment inflammation in central nervous system (CNS) through inhibiting Tob1. ..
  31. Ponnurangam S, Dandawate P, Dhar A, Tawfik O, Parab R, Mishra P, et al. Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells. Oncotarget. 2016;7:3217-32 pubmed publisher
    ..Together, these data suggest that Quinomycin is a potent inhibitor of pancreatic cancer that targets the stem cells by inhibiting Notch signaling proteins. ..
  32. Kim Y, Kim C, Son S, Song H, Hong H, Han S, et al. The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer's disease pathogenesis. Mol Neurodegener. 2016;11:4 pubmed publisher
    ..We provide evidence that PRAK plays a critical role in AD pathology as a key interactor of RAGE. Thus, our data suggest that PRAK might be a potential therapeutic target of AD involved in RAGE-mediated cell signaling induced by Aβ. ..
  33. Rota G, Ludigs K, Siegert S, Tardivel A, Morgado L, Reith W, et al. T Cell Priming by Activated Nlrc5-Deficient Dendritic Cells Is Unaffected despite Partially Reduced MHC Class I Levels. J Immunol. 2016;196:2939-46 pubmed publisher
  34. Chen Z, Wang S, Zhou J, Wu T, Li J. Contribution of PGR genetic polymorphisms to the pathogenesis of endometrial cancer: A meta-analysis. J Cancer Res Ther. 2015;11:810-7 pubmed publisher
    ..05). In conclusion, our findings provide empirical evidence that PGR rs1042838 and rs10895068 polymorphisms may be involved in the pathogenesis of endometrial cancer. ..
  35. Tame M, Raaijmakers J, Afanasyev P, Medema R. Chromosome misalignments induce spindle-positioning defects. EMBO Rep. 2016;17:317-25 pubmed publisher
    ..In summary, we uncovered a compelling molecular link between chromosome alignment and spindle orientation defects, both of which are implicated in tumorigenesis. ..
  36. Mazzoni J, Smith J, Shahriar S, Cutforth T, Ceja B, Agalliu D. The Wnt Inhibitor Apcdd1 Coordinates Vascular Remodeling and Barrier Maturation of Retinal Blood Vessels. Neuron. 2017;96:1055-1069.e6 pubmed publisher
    ..Apcdd1 thus serves to precisely modulate Wnt/Norrin signaling activity in the retinal endothelium and coordinate the timing of both vascular pruning and barrier maturation. ..
  37. Gueugnon F, Thibault V, Kearley J, Petit Courty A, Vallet A, Guillon A, et al. Altered expression of the CCN genes in the lungs of mice in response to cigarette smoke exposure and viral and bacterial infections. Gene. 2016;586:176-83 pubmed publisher
    ..Our findings reveal that several triggers of lung inflammation influence differently the CCN genes. CCN3 deserves special attention since its mRNA expression is decreased by all the triggers studied. ..
  38. Wang S, Hu T, Wang Z, Li N, Zhou L, Liao L, et al. Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure. PLoS ONE. 2017;12:e0185388 pubmed publisher
  39. Sumabat T, Hariharan I. Ras Brakes for Hippo. Dev Cell. 2017;42:561-562 pubmed publisher
    ..In this issue of Developmental Cell, Pascual and colleagues (2017) investigate the dire consequences of simultaneous deregulation of both the Ras and Hippo pathways. ..
  40. Lv X, Liu L, Cheng C, Yu B, Xiong L, Hu K, et al. SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer. Sci Rep. 2015;5:17940 pubmed publisher
  41. Han W, Liu J. Epigenetic silencing of the Wnt antagonist APCDD1 by promoter DNA hyper-methylation contributes to osteosarcoma cell invasion and metastasis. Biochem Biophys Res Commun. 2017;491:91-97 pubmed publisher
    ..Thus, we have provided the first evidence that APCDD1 expression is epigenetically silenced in OS, which may facilitate invasion and metastasis of OS cells. ..
  42. Nishimura T, Tamura N, Kono N, Shimanaka Y, Arai H, Yamamoto H, et al. Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER subdomains. EMBO J. 2017;36:1719-1735 pubmed publisher
    ..These findings suggest that the autophagy-initiation complex, the PIS-enriched ER subdomain, and ATG9A vesicles together initiate autophagosome formation. ..
  43. Katoh Y, Terada M, Nishijima Y, Takei R, Nozaki S, Hamada H, et al. Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex. J Biol Chem. 2016;291:10962-75 pubmed publisher
    ..The detailed interaction map as well as comparison of subcellular localization of IFT-B components between wild-type and Cluap1-deficient cells provides insights into the functional relevance of the architecture of the IFT-B complex. ..
  44. Dubois E, Gerber S, KISSELEV A, Harel Bellan A, Groisman R. UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis. Oncol Rep. 2016;35:3101-5 pubmed publisher
    ..Consistently, overexpression of a phosphorylation-resistant S474A CSN1 mutant reduced UV-induced apoptosis. Thus, CSN1 appears to play a role not only in DNA repair but also in UV-induced apoptosis. ..
  45. Xu H, Jiang W, Zhu F, Zhu C, Wei J, Wang J. Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival. APMIS. 2016;124:522-8 pubmed publisher
    ..The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma. ..
  46. Bengtsen M, Sørensen L, Aabel L, Ledsaak M, Matre V, Gabrielsen O. The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting p300 to chromatin. Biochim Biophys Acta Gene Regul Mech. 2017;1860:751-760 pubmed publisher
    ..We propose that ARA55 and HIPK1 assist c-Myb in recruiting the coactivator and acetyltransferase p300 to chromatin. ..
  47. Manzoni L, Samela A, Barbini S, Cairati S, Penconi M, Arosio D, et al. 4-Connected azabicyclo[5.3.0]decane Smac mimetics-Zn2+ chelators as dual action antitumoral agents. Bioorg Med Chem Lett. 2017;27:2336-2344 pubmed publisher
    ..In particular, the linker connecting DPA with the ABD scaffold seems to influence cellular Zn2+-chelation, with longer lipophilic linkers/DAC 3c being the optimal choice. ..
  48. Ying Q, Wu G. Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update. Ren Fail. 2017;39:474-483 pubmed publisher
    ..Therefore, the purpose of this paper is to update the research progress of these underlying signaling pathways and expound the podocyte EMT-related DKDs. ..
  49. Kim J, Kim Y, Kim J, Park D, Bae H, Lee D, et al. YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation. J Clin Invest. 2017;127:3441-3461 pubmed publisher
  50. Yang Q, Liu T, Lin H, Zhang M, Wei J, Luo W, et al. TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. PLoS Pathog. 2017;13:e1006600 pubmed publisher
    ..Furthermore, TRIM32 links TRIF and TAX1BP1 through distinct domains. These findings suggest that TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TRIF to TAX1BP1-mediated selective autophagic degradation. ..
  51. Neve A, Trüb J, Saxena S, Schümperli D. Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice. Mol Cell Neurosci. 2016;70:30-41 pubmed publisher
  52. Zemankova N, Chlebova K, Matiasovic J, Prodělalová J, Gebauer J, Faldyna M. Bovine lactoferrin free of lipopolysaccharide can induce a proinflammatory response of macrophages. BMC Vet Res. 2016;12:251 pubmed
    ..Our results suggest that LF's ability is not only to bind LPS, but LF itself may be a stimulant of pro-inflammatory pathways. ..
  53. Zhang J, Tan X, Yuan Z, Li Y, Qi Y, Nan X, et al. [Let-7 miRNA silencing promotes Kaposi's sarcoma-associated herpesvirus lytic replication via activating mitogen-activated protein kinase kinase kinase kinase 4 and its downstream factors]. Zhonghua Zhong Liu Za Zhi. 2016;38:485-91 pubmed publisher
    ..Let-7 silencing may activate the replication of KSHV, possibly through up-regulating MAP4K4 and its downstream molecules COX-2, MMP-13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma. ..