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Gene Review

FBXO32  -  F-box protein 32

Homo sapiens

Synonyms: ATROGIN1, Atrogin-1, F-box only protein 32, Fbx32, MAFbx, ...
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Disease relevance of FBXO32

  • Atrogin-1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases [1].
  • Therefore, here we have shown that FBXO25 is a novel F-box protein analogous to atrogin-1, which is not involved in muscle atrophy [2].
  • In cardiac hypertrophy, Atrogin1 and MuRF1 attenuate cardiac hypertrophy by interacting with calcineurin and PKCepsilon, respectively [3].
  • Additionally, peritonitis produced by cecal ligation and puncture increased atrogin-1 and MuRF1 mRNA in gastrocnemius (but not soleus or heart) by 8 h, which was sustained for 72 and 24 h, respectively [4].
  • The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy [5].

High impact information on FBXO32

  • This perspective will focus on the signalling pathways that control skeletal muscle atrophy and hypertrophy, including the recently identified ubiquitin ligases muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx), as a basis to develop targets for pharmacologic intervention in muscle disease [6].
  • Transfection of PGC-1alpha into adult fibers reduced the capacity of FoxO3 to cause fiber atrophy and to bind to and transcribe from the atrogin-1 promoter [7].
  • Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity [8].
  • The expression of MAFbx/Murf-1 and troponin I was analyzed by RT-PCR and Western blotting in the non-infarcted area of the left ventricle [9].
  • Our results showed that, despite the presence of TNF-alpha/IFN-gamma, IGF-I retained its full ability to induce the phosphorylation of Akt, Foxo3a, and GSK-3beta (respectively, 16-fold, 9-fold, and 2-fold) together with a decrease in atrogin-1 mRNA (-39%, P < 0.001) [10].

Biological context of FBXO32

  • IGF-I rapidly reduced atrogin-1 expression within 1 h by blocking mRNA synthesis without affecting mRNA degradation, whereas IGF-I decreased MuRF1 mRNA slowly [11].
  • Subjects underwent a percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3) individual fiber type and cross-sectional area [12].
  • Atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 are associated with uterine smooth muscle involution in the postpartum period [13].
  • The findings indicate an important role for the immediate upstream promotor of the human MAFbx gene in mediating its developmental expression and tissue specificity [14].
  • This study evaluated the effect of ES based on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in denervated tibialis anterior (TA) muscle of Wistar rats [15].

Anatomical context of FBXO32

  • In myotubes, dexamethasone (Dex) inhibited growth and enhanced breakdown of long-lived cell proteins, especially myofibrillar proteins (as measured by 3-methylhistidine release), while also increasing atrogin-1 and MuRF1 mRNA [11].
  • Here we show that atrogin-1 is also expressed in smooth muscle, and that both atrogin-1 and MuRF-1 are upregulated in the uterus following delivery, as rapid involution occurs [13].
  • A biopsy was obtained from the sternohyoid muscle in patients undergoing surgery for primary HPT (n=8) and in normocalcemic control patients undergoing thyroid surgery (n=11). mRNA levels for atrogin-1, MuRF1 and the calcium-regulated proteases, mu- and m-calpain, were determined by real-time PCR [16].
  • To gain insights into mechanisms by which the human MAFbx gene is controlled, the structure of its upstream promotor were studied, and its expression in cultured cells was characterized [14].

Associations of FBXO32 with chemical compounds


Regulatory relationships of FBXO32


Other interactions of FBXO32

  • Further work has demonstrated a trigger for MAFbx expression upon treatment with TNFalpha--the p38 MAPK pathway [21].
  • Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection [22].
  • IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA [10].
  • In addition, we measured transcript levels of genes known to regulate skeletal muscle atrophy, all of which are negatively regulated by IGF-1 (Mafbx/Atrogin-1, MuRF-1) [23].
  • Atrophy in striated muscle results from enhanced protein breakdown and is associated with a common transcriptional profile and activation of the ubiquitin-proteasome pathway, including induction of the muscle-specific ubiquitin protein ligases atrogin-1 and muscle ring-finger protein 1 (MuRF-1) [13].

Analytical, diagnostic and therapeutic context of FBXO32

  • Using a RT-PCR, we demonstrated that FBXO25 is highly expressed in brain, kidney, and intestine, whereas atrogin-1 expression is largely restricted to striate muscle [2].
  • After 48 h of burn injury (40% total body surface area full-thickness scald burn) gastrocnemius weight was reduced, and this change was associated with an increased mRNA abundance for atrogin-1 and MuRF-1 (3.1- to 8-fold, respectively) [18].
  • Furthermore, in transgenic mice overexpressing PGC-1alpha, denervation and fasting caused a much smaller decrease in muscle fiber diameter and a smaller induction of atrogin-1 and MuRF-1 than in control mice [7].
  • In cell culture experiments the potency of TNF-alpha to stimulate Murf-1/MAFbx expression, the intracellular signaling pathway, and the involvement of the E3-ligases for the impairment of contractility were assessed [9].
  • A real-time reverse transcription-polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl-b and atrogin-1 [24].


  1. Akt signalling through GSK-3{beta}, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. L??ger, B., Cartoni, R., Praz, M., Lamon, S., D??riaz, O., Crettenand, A., Gobelet, C., Rohmer, P., Konzelmann, M., Luthi, F., Russell, A.P. J. Physiol. (Lond.) (2006) [Pubmed]
  2. FBXO25, an F-box protein homologue of atrogin-1, is not induced in atrophying muscle. Maragno, A.L., Baqui, M.M., Gomes, M.D. Biochim. Biophys. Acta (2006) [Pubmed]
  3. Into the heart: The emerging role of the ubiquitin-proteasome system. Willis, M.S., Patterson, C. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  4. Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle. Frost, R.A., Nystrom, G.J., Jefferson, L.S., Lang, C.H. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  5. Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis. Stein, T.P., Wade, C.E. Current opinion in clinical nutrition and metabolic care. (2003) [Pubmed]
  6. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Glass, D.J. Nat. Cell Biol. (2003) [Pubmed]
  7. PGC-1{alpha} protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z.P., Lecker, S.H., Goldberg, A.L., Spiegelman, B.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Gilson, H., Schakman, O., Combaret, L., Lause, P., Grobet, L., Attaix, D., Ketelslegers, J.M., Thissen, J.P. Endocrinology (2007) [Pubmed]
  9. Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility. Adams, V., Linke, A., Wisloff, U., D??ring, C., Erbs, S., Kr??nkel, N., Witt, C.C., Labeit, S., M??ller-Werdan, U., Schuler, G., Hambrecht, R. Cardiovasc. Res. (2007) [Pubmed]
  10. IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA. Dehoux, M., Gobier, C., Lause, P., Bertrand, L., Ketelslegers, J.M., Thissen, J.P. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  11. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Sacheck, J.M., Ohtsuka, A., McLary, S.C., Goldberg, A.L. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  12. Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age. Whitman, S.A., Wacker, M.J., Richmond, S.R., Godard, M.P. Pflugers Arch. (2005) [Pubmed]
  13. Atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 are associated with uterine smooth muscle involution in the postpartum period. Bdolah, Y., Segal, A., Tanksale, P., Karumanchi, S.A., Lecker, S.H. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
  14. Structure and function of the upstream promotor of the human Mafbx gene: the proximal upstream promotor modulates tissue-specificity. Zhao, W., Wu, Y., Zhao, J., Guo, S., Bauman, W.A., Cardozo, C.P. J. Cell. Biochem. (2005) [Pubmed]
  15. Electrical stimulation based on chronaxie reduces atrogin-1 and myoD gene expressions in denervated rat muscle. Russo, T.L., Peviani, S.M., Freria, C.M., Gigo-Benato, D., Geuna, S., Salvini, T.F. Muscle Nerve (2007) [Pubmed]
  16. The gene expression and activity of calpains and the muscle wasting-associated ubiquitin ligases, atrogin-1 and MuRF1, are not altered in patients with primary hyperparathyroidism. Evenson, A., Mitchell, J., Wei, W., Poylin, V., Parangi, S., Hasselgren, P.O. Int. J. Mol. Med. (2006) [Pubmed]
  17. Molecular signaling pathways regulating muscle proteolysis during atrophy. Franch, H.A., Price, S.R. Current opinion in clinical nutrition and metabolic care. (2005) [Pubmed]
  18. Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I. Lang, C.H., Huber, D., Frost, R.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
  19. Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats. Granado, M., Mart??n, A.I., Priego, T., L??pez-Calder??n, A., Villan??a, M.A. J. Endocrinol. (2006) [Pubmed]
  20. Expression of the muscle atrophy factor muscle atrophy F-box is suppressed by testosterone. Zhao, W., Pan, J., Wang, X., Wu, Y., Bauman, W.A., Cardozo, C.P. Endocrinology (2008) [Pubmed]
  21. Skeletal muscle hypertrophy and atrophy signaling pathways. Glass, D.J. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  22. Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection. Molina, P.E., McNurlan, M., Rathmacher, J., Lang, C.H., Zambell, K.L., Purcell, J., Bohm, R.P., Zhang, P., Bagby, G.J., Nelson, S. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  23. Atrophic remodeling of the transplanted rat heart. Sharma, S., Ying, J., Razeghi, P., Stepkowski, S., Taegtmeyer, H. Cardiology (2006) [Pubmed]
  24. Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest. Ogawa, T., Furochi, H., Mameoka, M., Hirasaka, K., Onishi, Y., Suzue, N., Oarada, M., Akamatsu, M., Akima, H., Fukunaga, T., Kishi, K., Yasui, N., Ishidoh, K., Fukuoka, H., Nikawa, T. Muscle Nerve (2006) [Pubmed]
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