CARM1
| coactivator-associated arginine methyltransferase 1 | |||||||
|---|---|---|---|---|---|---|---|
Struktur Kristal Coactivator Associated Arginine Methyltransferase 1[1] | |||||||
| Pengidentifikasi | |||||||
| Simbol | CARM1 | ||||||
| Gen NCBI | 10498 | ||||||
| HGNC | 23393 | ||||||
| OMIM | 603934 | ||||||
| RefSeq | XM_032719 | ||||||
| UniProt | Q86X55 | ||||||
| Data lain | |||||||
| Nomor EC | 2.1.1.125 | ||||||
| Lokus | Chr. 19 p13.2 | ||||||
| |||||||
| coactivator associated arginine methyltransferase 1-like | |||||||
|---|---|---|---|---|---|---|---|
| Pengidentifikasi | |||||||
| Simbol | CARM1L | ||||||
| Gen NCBI | 256280 | ||||||
| HGNC | 23392 | ||||||
| RefSeq | XM_171224 | ||||||
| UniProt | Q5SZY8 | ||||||
| Data lain | |||||||
| Lokus | Chr. 9 p24.2 | ||||||
| |||||||
CARM1 (coactivator-associated arginine methyltransferase 1), yang juga dikenal sebagai PRMT4 (protein arginine N-methyltransferase 4), adalah suatu enzim (EC 2.1.1.125) yang dikodekan oleh gen CARM1 yang ditemukan pada manusia, serta banyak mamalia lainnya.[2] Enzim ini memiliki tipe rantai polipeptida (L) sepanjang 348 residu, dan tersusun atas heliks alfa dan lembaran beta.[3] Fungsi utamanya mencakup mengatalisis transfer gugus metil dari S-Adenosil metionin ke nitrogen rantai samping residu arginina di dalam protein untuk membentuk turunan arginina termetilasi dan S-Adenosil-L-homosistein.[4] CARM1 adalah koaktivator sekunder melalui asosiasinya dengan koaktivator keluarga p160 (SRC-1, GRIP1, AIB). Enzim ini bertanggung jawab untuk menggerakkan sel menuju massa sel dalam pada blastokista yang sedang berkembang.[5]
Signifikansi klinis
CARM1 memainkan peran penting pada reseptor androgen dan mungkin berperan dalam perkembangan kanker prostat.[6][7]
CARM1 menjalankan fungsi onkogenik sekaligus penekan tumor. Pada kanker payudara, CARM1 memetilasi faktor remodelasi kromatin BAF155 untuk meningkatkan perkembangan tumor dan metastasis.[8] Pada kanker pankreas, CARM1 memetilasi dan menghambat MDH1 dengan mengganggu dimerisasinya, yang menekan respirasi mitokondria dan menghambat pemanfaatan glutamin. Metilasi MDH1 yang dimediasi CARM1 menurunkan kadar NADPH seluler dan membuat sel lebih sensitif terhadap stres oksidatif, sehingga menekan proliferasi sel dan pembentukan koloni.[9]
Lihat pula
Pranala luar
Referensi
- ^ "RCSB Protein Data Bank - Structure Summary for 2Y1W - CRYSTAL STRUCTURE OF COACTIVATOR ASSOCIATED ARGININE METHYLTRANSFERASE 1 (CARM1) IN COMPLEX WITH SINEFUNGIN AND INDOLE INHIBITOR".
- ^ Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR (1999). "Regulation of transcription by a protein methyltransferase". Science. 284 (5423): 2174–7. doi:10.1126/science.284.5423.2174. PMID 10381882.
- ^ "RCSB Protein Data Bank - Sequence / Structure Details for 2Y1W - CRYSTAL STRUCTURE OF COACTIVATOR ASSOCIATED ARGININE METHYLTRANSFERASE 1 (CARM1) IN COMPLEX WITH SINEFUNGIN AND INDOLE INHIBITOR". Diarsipkan dari asli tanggal 2015-09-24. Diakses tanggal 2011-04-13.
- ^ "CARM1 Gene - GeneCards | CARM1 Protein | CARM1 Antibody".
- ^ Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M (2007). "Histone arginine methylation regulates pluripotency in the early mouse embryo". Nature. 445 (7124): 214–8. Bibcode:2007Natur.445..214T. doi:10.1038/nature05458. PMC 3353120. PMID 17215844.
- ^ Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, Zhang S, Li L, Pan CX, Hu Z, MacLennan GT, Cheng L (2004). "Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status". Cancer. 101 (1): 83–9. doi:10.1002/cncr.20327. PMID 15221992. S2CID 274474.
- ^ Majumder S, Liu Y, Ford OH, Mohler JL, Whang YE (2006). "Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability". Prostate. 66 (12): 1292–301. doi:10.1002/pros.20438. PMID 16705743. S2CID 23950904.
- ^ Wang L, Zhao Z, Meyer MB, Saha S, Yu M, Guo A, Wisinski KB, Huang W, Cai W, Pike JW, Yuan M, Ahlquist P, Xu W (Jul 2016). "CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis". Cancer Cell. 30 (1): 179–180. doi:10.1016/j.ccr.2013.12.007. PMC 4004525. PMID 24434208.
- ^ Wang YP, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, Gao X, Xu YY, Zou SW, Liu YB, Cheng JK, Lei QY (Nov 2016). "Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer". Molecular Cell. 64 (4): 673–87. doi:10.1016/j.molcel.2016.09.028. PMID 27840030.
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