Reviewed November 2013
What are the PSM genes?
Genes in the PSM family provide instructions for making parts (subunits) of cell structures called proteasomes. Proteasomes are large complexes that recognize and break down (degrade) unneeded, excess, or abnormal proteins as part of the cell's quality control system. The degradation of proteins by proteasomes is essential for many fundamental cell processes, including regulation of the amount of various proteins in cells (protein homeostasis), cell growth and division, the process by which cells mature to carry out specific functions (differentiation), chemical signaling within cells, and the activity of genes.
Although proteasomes are found in cells throughout the body, researchers have discovered at least two specialized types of proteasomes that are specific to certain cells and tissues. Immunoproteasomes are located primarily in immune system cells, where they play an important role in regulating the immune system's response to foreign invaders, such as viruses and bacteria. Thymoproteasomes are found only in the thymus, which is a gland located behind the breastbone that produces white blood cells called lymphocytes. Immunoproteasomes and thymoproteasomes include several subunits that are not part of regular proteasomes; these subunits are also produced from genes in the PSM family.
One PSM family gene, PSMB8, has been found to cause at least three similar conditions with overlapping signs and symptoms. These conditions are Nakajo-Nishimura syndrome; joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome; and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. The PSMB8 gene provides instructions for making a subunit that is specific to immunoproteasomes. Through mechanisms that are unclear, mutations in this gene lead to malfunction of the immune system, which triggers abnormal inflammation that can damage tissues throughout the body.
Which genes are included in the PSM gene family?
The HUGO Gene Nomenclature Committee (HGNC) provides an index of gene families (http://www.genenames.org/cgi-bin/genefamilies/) and their member genes.
Genetics Home Reference summarizes the normal function and health implications of this member of the PSM gene family: PSMB8.
What conditions are related to genes in the PSM gene family?
Genetics Home Reference includes these conditions related to genes in the PSM gene family:
- Nakajo-Nishimura syndrome
Where can I find additional information about
the PSM gene family?
You may find the following resources about the PSM gene family helpful.
- Howard Hughes Medical Institute: The Proteasome and Protein Regulation (http://www.hhmi.org/biointeractive/proteasome-and-protein-regulation)
- Biochemistry (fifth edition, 2002): The Proteasome Digests the Ubiquitin-Tagged Proteins (http://www.ncbi.nlm.nih.gov/books/NBK22397/)
- The Cell: A Molecular Approach (second edition, 2000): Protein Degradation (http://www.ncbi.nlm.nih.gov/books/NBK9957/)
What glossary definitions help with understanding the PSM gene family?
immune system ;
microcytic anemia ;
white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference
These sources were used to develop the Genetics Home Reference summary for the PSM gene family.
- Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T, Mizushima T, Ichinose K, Nakamura H, Tsujino A, Kawakami A, Matsunaka M, Kasagi S, Kawano S, Kumagai S, Ohmura K, Mimori T, Hirano M, Ueno S, Tanaka K, Tanaka M, Toyoshima I, Sugino H, Yamakawa A, Tanaka K, Niikawa N, Furukawa F, Murata S, Eguchi K, Ida H, Yoshiura K. Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome. Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14914-9. doi: 10.1073/pnas.1106015108. Epub 2011 Aug 18. (http://www.ncbi.nlm.nih.gov/pubmed/21852578?dopt=Abstract)
- Agarwal AK, Xing C, DeMartino GN, Mizrachi D, Hernandez MD, Sousa AB, Martínez de Villarreal L, dos Santos HG, Garg A. PSMB8 encoding the β5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet. 2010 Dec 10;87(6):866-72. doi: 10.1016/j.ajhg.2010.10.031. (http://www.ncbi.nlm.nih.gov/pubmed/21129723?dopt=Abstract)
- Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K. A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest. 2011 Oct;121(10):4150-60. doi: 10.1172/JCI58414. Epub 2011 Sep 1. (http://www.ncbi.nlm.nih.gov/pubmed/21881205?dopt=Abstract)
- Jung T, Grune T. Structure of the proteasome. Prog Mol Biol Transl Sci. 2012;109:1-39. doi: 10.1016/B978-0-12-397863-9.00001-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22727418?dopt=Abstract)
- Tanaka K, Mizushima T, Saeki Y. The proteasome: molecular machinery and pathophysiological roles. Biol Chem. 2012 Apr;393(4):217-34. doi: 10.1515/hsz-2011-0285. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23029643?dopt=Abstract)
- Saeki Y, Tanaka K. Assembly and function of the proteasome. Methods Mol Biol. 2012;832:315-37. doi: 10.1007/978-1-61779-474-2_22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22350895?dopt=Abstract)
- Murata S, Sasaki K, Kishimoto T, Niwa S, Hayashi H, Takahama Y, Tanaka K. Regulation of CD8+ T cell development by thymus-specific proteasomes. Science. 2007 Jun 1;316(5829):1349-53. (http://www.ncbi.nlm.nih.gov/pubmed/17540904?dopt=Abstract)
- Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, Kim PW, Sheikh A, Lee CC, Chen Y, Vera A, Zhang X, Goldbach-Mansky R, Zlotogorski A. Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012 Mar;64(3):895-907. doi: 10.1002/art.33368. (http://www.ncbi.nlm.nih.gov/pubmed/21953331?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.