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Gene Review

NAIP  -  NLR family, apoptosis inhibitory protein

Homo sapiens

Synonyms: BIRC1, Baculoviral IAP repeat-containing protein 1, NLRB1, Neuronal apoptosis inhibitory protein, psiNAIP
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Disease relevance of NAIP


Psychiatry related information on NAIP


High impact information on NAIP


Biological context of NAIP

  • Interestingly, and in contrast to the X-chromosome-linked inhibitor of apoptosis protein (XIAP), NAIP-mediated inhibition of caspase-9 was not countered by a peptide containing an amino-terminal IAP binding motif (IBM) [10].
  • Study of survival of motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) gene deletions in SMA patients [11].
  • In the view of scarcity of genotype and phenotype correlation data from India, this study has been undertaken to determine that correlation in SMA patients by using the SMN and NAIP genes and two polymorphic markers C212 and C272 located in this region [12].
  • Taken together with our previous data, we may reasonably hypothesize that the SMN2 gene copy number is more critical in determining the severity of the disease compared to the NAIP genotype [3].
  • In the period 1998-2000 almost all new cases of childhood spinal muscular atrophy (SMA) in addition to those from our database were studied for possible deletion of SMN gene (exons 7 a 8) and NAIP (exons 5 a 6) [13].

Anatomical context of NAIP

  • These molecules can prevent apoptosis in vitro and the over-expression of NAIP can decrease ischemic damage in the hippocampus [14].
  • The goal of our experiments was to determine whether administration of NAIP, HIAP1 and HAIP2 could rescue motoneurons following axotomy of a peripheral nerve [14].
  • NAIP-like immunoreactivity was determined in four different regions of cerebral cortex and cerebellum in 9 adult DS patients with Alzheimer-like neuropathologic lesions, 9 Alzheimer disease (AD) patients as compared to 9 controls [2].
  • In contrast, NAIP mRNA was not detectable, and cIAP2 was found at the mRNA and protein levels in only 34 (56%) and 5 (8%) of the 60 tumor cell lines analyzed, respectively [15].
  • As for age-related changes, the expression of cIAP2 in normal mucosa and moderately differentiated adenocarcinoma was stronger in the elderly group than the young group ( p<0.05, respectively), and NAIP expression in well-differentiated adenocarcinoma was higher in the young group than the elderly group ( p<0.05) [16].

Associations of NAIP with chemical compounds

  • In neuronal cell lines NSC-34 and Neuro-2a, over-expression of the BIR domains of NAIP (NAIP-BIR1-3) counteracted the calcium-induced cell death induced by ionomycin and thapsigargin [17].
  • Cisplatin decreased NAIP and survivin mRNAs in the same cells [18].
  • IB-MECA 100 microM downregulated HIAP1, NAIP and survivin mRNAs in HL-60, but not in HL-60R cells [19].
  • The cytotoxic interactions between curcumin and these agents were accompanied by synergistic (in particular with cisplatin) or additive effects of decrease in the expression of different genes, including c-myc, Bcl-X(L), c-IAP-2, NAIP and XIAP [20].
  • These observations suggest that the powerful effects of PAX2 on renal branching morphogenesis and final nephron number may be mediated by activation of Naip which then suppresses apoptosis in UB cells [21].

Physical interactions of NAIP

  • Consistent with this observation was the failure of Smac protein to interact with the NAIP BIR domains [10].
  • NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways [17].

Regulatory relationships of NAIP


Other interactions of NAIP

  • Here we report that two other members of the IAP family, NAIP and ML-IAP, both activate JNK1 [23].
  • Both SMN1 and NAIP genes showed homozygous absence in 76% and 31% respectively in proximal SMA patients [11].
  • It also decreased interleukin 6 (IL-6), NAIP and, after 16 h of exposure to the higher concentration tested (10 microg/ml), c-IAP-1 mRNA levels [24].
  • In this report, we examined the interaction of various regions of NAIP with caspase-9 and Smac [10].
  • Recombinant c-IAP-1 and c-IAP-2 also inhibited the activity of caspases-3 and -7 in vitro, with estimated Kis of <=0.1 microM, whereas NAIP did not [25].

Analytical, diagnostic and therapeutic context of NAIP

  • The administration of an adv-NAIP, adv-HIAP1 and adv-HIAP2 rescued 30-40% of motoneurons at one week after sciatic axotomy [14].
  • Furthermore, RT-PCR analysis reveals internally deleted and mutated forms of the NAIP transcript in type I SMA individuals and not in unaffected individuals [7].
  • We examined the endogenous expression of four members of the IAP family, X chromosome-linked IAP (XIAP), rat IAP1 (RIAP1), RIAP2, and neuronal apoptosis inhibitory protein (NAIP), by semiquantitative reverse PCR and immunoblot analysis in cultured cerebellar granule neurons [26].
  • Prenatal diagnosis of childhood proximal spinal muscular atrophy (SMA) is carried out by the detection of homozygous deletions of survival motor neuron (SMN; exons 7 and 8) and neuronal apoptosis inhibitory protein (NAIP; exons 5 and 6) genes located in 5q13 chromosomal region [27].
  • These data suggest that the NAIP upregulating compound, L-745,870, has therapeutic potential in acute ischemic disorders and that our NAIP-ELISA-based drug screening may facilitate the discovery of novel neuroprotective compounds [22].


  1. Extensive DNA deletion associated with severe disease alleles on spinal muscular atrophy homologues. Wang, C.H., Carter, T.A., Das, K., Xu, J., Ross, B.M., Penchaszadeh, G.K., Gilliam, T.C. Ann. Neurol. (1997) [Pubmed]
  2. Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome. Seidl, R., Bajo, M., Böhm, K., LaCasse, E.C., MacKenzie, A.E., Cairns, N., Lubec, G. J. Neural Transm. Suppl. (1999) [Pubmed]
  3. Significant increase in the number of the SMN2 gene copies in an adult-onset Type III spinal muscular atrophy patient with homozygous deletion of the NAIP gene. Yamashita, M., Nishio, H., Harada, Y., Matsuo, M., Yamamoto, T. Eur. Neurol. (2004) [Pubmed]
  4. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Liston, P., Roy, N., Tamai, K., Lefebvre, C., Baird, S., Cherton-Horvat, G., Farahani, R., McLean, M., Ikeda, J.E., MacKenzie, A., Korneluk, R.G. Nature (1996) [Pubmed]
  5. Adipogenic and antiapoptotic protein levels in human adipose stromal cells after weight loss. Aubin, D., Gagnon, A., Grunder, L., Dent, R., Allen, M., Sorisky, A. Obes. Res. (2004) [Pubmed]
  6. Differential regulation of inhibitors of apoptosis proteins in Alzheimer's disease brains. Christie, L.A., Su, J.H., Tu, C.H., Dick, M.C., Zhou, J., Cotman, C.W. Neurobiol. Dis. (2007) [Pubmed]
  7. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Roy, N., Mahadevan, M.S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X. Cell (1995) [Pubmed]
  8. Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy. Iwahashi, H., Eguchi, Y., Yasuhara, N., Hanafusa, T., Matsuzawa, Y., Tsujimoto, Y. Nature (1997) [Pubmed]
  9. IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo. Perrelet, D., Ferri, A., Liston, P., Muzzin, P., Korneluk, R.G., Kato, A.C. Nat. Cell Biol. (2002) [Pubmed]
  10. Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9. Davoodi, J., Lin, L., Kelly, J., Liston, P., MacKenzie, A.E. J. Biol. Chem. (2004) [Pubmed]
  11. Study of survival of motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) gene deletions in SMA patients. Kesari, A., Misra, U.K., Kalita, J., Mishra, V.N., Pradhan, S., Patil, S.J., Phadke, S.R., Mittal, B. J. Neurol. (2005) [Pubmed]
  12. Genotype-phenotype correlation of SMN locus genes in spinal muscular atrophy patients from India. Kesari, A., Idris, M.M., Chandak, G.R., Mittal, B. Exp. Mol. Med. (2005) [Pubmed]
  13. Phenotype and genotype correlation in childhood spinal muscular atrophy. Hausmanowa-Petrusewicz, I. Neurologia i neurochirurgia polska. (2001) [Pubmed]
  14. IAP family proteins delay motoneuron cell death in vivo. Perrelet, D., Ferri, A., MacKenzie, A.E., Smith, G.M., Korneluk, R.G., Liston, P., Sagot, Y., Terrado, J., Monnier, D., Kato, A.C. Eur. J. Neurosci. (2000) [Pubmed]
  15. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Tamm, I., Kornblau, S.M., Segall, H., Krajewski, S., Welsh, K., Kitada, S., Scudiero, D.A., Tudor, G., Qui, Y.H., Monks, A., Andreeff, M., Reed, J.C. Clin. Cancer Res. (2000) [Pubmed]
  16. Expression of IAP family proteins in colon cancers from patients with different age groups. Endo, T., Abe, S., Seidlar, H.B., Nagaoka, S., Takemura, T., Utsuyama, M., Kitagawa, M., Hirokawa, K. Cancer Immunol. Immunother. (2004) [Pubmed]
  17. NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways. Mercer, E.A., Korhonen, L., Skoglösa, Y., Olsson, P.A., Kukkonen, J.P., Lindholm, D. EMBO J. (2000) [Pubmed]
  18. Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and of the novel anti-apoptosis factors IAP (inhibitory of apoptosis proteins). Notarbartolo, M., Cervello, M., Dusonchet, L., Cusimano, A., D'Alessandro, N. Cancer Lett. (2002) [Pubmed]
  19. Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effects on inhibitor of apoptosis protein levels. Notarbartolo, M., Lo Cicero, S., Meli, M., Poma, P., Labbozzetta, M., Cervello, M., D'Alessandro, N. Chemotherapy. (2005) [Pubmed]
  20. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Notarbartolo, M., Poma, P., Perri, D., Dusonchet, L., Cervello, M., D'Alessandro, N. Cancer Lett. (2005) [Pubmed]
  21. Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2. Dziarmaga, A., Hueber, P.A., Iglesias, D., Hache, N., Jeffs, A., Gendron, N., Mackenzie, A., Eccles, M., Goodyer, P. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  22. A dopamine D4 receptor antagonist attenuates ischemia-induced neuronal cell damage via upregulation of neuronal apoptosis inhibitory protein. Okada, Y., Sakai, H., Kohiki, E., Suga, E., Yanagisawa, Y., Tanaka, K., Hadano, S., Osuga, H., Ikeda, J.E. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  23. IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition. Sanna, M.G., da Silva Correia, J., Ducrey, O., Lee, J., Nomoto, K., Schrantz, N., Deveraux, Q.L., Ulevitch, R.J. Mol. Cell. Biol. (2002) [Pubmed]
  24. Antitumor effects of the novel NF-kappaB inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production. Poma, P., Notarbartolo, M., Labbozzetta, M., Sanguedolce, R., Alaimo, A., Carina, V., Maurici, A., Cusimano, A., Cervello, M., D'Alessandro, N. Int. J. Oncol. (2006) [Pubmed]
  25. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Roy, N., Deveraux, Q.L., Takahashi, R., Salvesen, G.S., Reed, J.C. EMBO J. (1997) [Pubmed]
  26. Adenovirus-mediated gene transfer of inhibitors of apoptosis protein delays apoptosis in cerebellar granule neurons. Simons, M., Beinroth, S., Gleichmann, M., Liston, P., Korneluk, R.G., MacKenzie, A.E., Bähr, M., Klockgether, T., Robertson, G.S., Weller, M., Schulz, J.B. J. Neurochem. (1999) [Pubmed]
  27. Prenatal diagnosis of spinal muscular atrophy in Turkish families. Erdem, H., Dayangaç, D., Pehlivan, S., Topaloglu, H. Cent. Eur. J. Public Health (2001) [Pubmed]
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