PRDM16
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Location (UCSC) | Chr 1: 3.07 – 3.44 Mb | Chr 4: 154.4 – 154.72 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
PR domain containing 16, also known as PRDM16, is a protein which in humans is encoded by the PRDM16 gene.[5][6]
PRDM16 acts as a transcription coregulator that controls the development of brown adipocytes in brown adipose tissue.[7] Previously, this coregulator was believed to be present only in brown adipose tissue, but more recent studies have shown that PRDM16 is highly expressed in subcutaneous white adipose tissue as well.[7]
Function
The protein encoded by this gene is a zinc finger transcription factor.[6] PRDM16 controls the cell fate between muscle and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation.[8]
Clinical significance
The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36;q21)-positive MDS/AML. The protein encoded by this gene contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported.[6]
PRDM16 in BAT
Brown adipose tissue (BAT) oxidizes chemical energy to produce heat. This heat energy can act as a defense against hypothermia and obesity.
PRDM16 in WAT
White adipose tissue (WAT) primarily stores excess energy in the form of triglycerides.[7][9] Recent research has shown that PRDM16 is present in subcutaneous white adipose tissue.[7] The activity of PRDM16 in white adipose tissue leads to the production of brown fat-like adipocytes within white adipose tissue, called beige cells (also called brite cells). These beige cells have a brown adipose tissue-like phenotype and actions, including thermogenic processes seen in BAT.[7] In mice, the levels of PRDM16 within WAT, specifically anterior subcutaneous WAT and inguinal subcutaneous WAT, is about 50% that of interscapular BAT, both in protein expression and in mRNA quantity.[7] This expression takes place primarily within mature adipocytes.
If human WAT expresses PRDM16 as in mice, this WAT could be a potential target for stimulating energy expenditure and combating obesity.
Notes
- ^ a b c GRCh38: Ensembl release 89: ENSG00000142611 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039410 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 11050005.
- ^ a b c "Entrez Gene: PRDM16 PR domain containing 16".
- ^ PMID 21123942.
- PMID 18719582.
- ^ PMID 17618855.
References
- This article incorporates text from the United States National Library of Medicine, which is in the public domain.
- Kajimura S (2009). "Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex". Nature. 460 (7259): 1154–1158. PMID 19641492.
Further reading
- Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. PMID 12168954.
- Bloomfield CD, Garson OM, Volin L, et al. (1986). "t(1;3)(p36;q21) in acute nonlymphocytic leukemia: a new cytogenetic-clinicopathologic association". Blood. 66 (6): 1409–13. PMID 4063527.
- Secker-Walker LM, Mehta A, Bain B (1996). "Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study". Br. J. Haematol. 91 (2): 490–501. S2CID 23922912.
- Mochizuki N, Shimizu S, Nagasawa T, et al. (2000). "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells". Blood. 96 (9): 3209–14. PMID 11050005.
- Nagase T, Kikuno R, Hattori A, et al. (2001). "Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (6): 347–55. PMID 11214970.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Xinh PT, Tri NK, Nagao H, et al. (2003). "Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1". Genes Chromosomes Cancer. 36 (3): 313–6. S2CID 36946681.
- Nishikata I, Sasaki H, Iga M, et al. (2004). "A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation". Blood. 102 (9): 3323–32. PMID 12816872.
- Yoshida M, Nosaka K, Yasunaga J, et al. (2004). "Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells". Blood. 103 (7): 2753–60. PMID 14656887.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. PMID 14702039.
- Lahortiga I, Agirre X, Belloni E, et al. (2004). "Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells". Oncogene. 23 (1): 311–6. PMID 14712237.
- Ott MG, Schmidt M, Schwarzwaelder K, et al. (2006). "Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1". Nat. Med. 12 (4): 401–9. S2CID 7601162.
- Stevens-Kroef MJ, Schoenmakers EF, van Kraaij M, et al. (2006). "Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML". Leukemia. 20 (6): 1187–9. S2CID 40770542.
- Stiffler MA, Grantcharova VP, Sevecka M, MacBeath G (2007). "Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays". J. Am. Chem. Soc. 128 (17): 5913–22. PMID 16637659.
External links
- PRDM16+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)