Structure specific recognition protein 1 explained

FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.^[1]

Function

The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63.

Interactions

Structure specific recognition protein 1 has been shown to interact with NEK9.^[2] SSRP1 further interacts with transcriptional activator p63.^[3] SSRP1 enhances the activity of full-length p63, but it has no effect on the N-terminus-deleted p63 (DeltaN-p63) variant.

Further reading

• Bruhn SL, Pil PM, Essigmann JM, Housman DE, Lippard SJ . Isolation and characterization of human cDNA clones encoding a high mobility group box protein that recognizes structural distortions to DNA caused by binding of the anticancer agent cisplatin. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 6 . 2307–11 . 1992 . 1372440 . 48646 . 10.1073/pnas.89.6.2307 . 1992PNAS...89.2307B . free .
• Toney JH, Donahue BA, Kellett PJ, Bruhn SL, Essigmann JM, Lippard SJ . Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diamminedichloroplatinum(II) . Proc. Natl. Acad. Sci. U.S.A. . 86 . 21 . 8328–32 . 1989 . 2530581 . 298274 . 10.1073/pnas.86.21.8328 . 1989PNAS...86.8328T . free .
• Nagulapalli S, Pongubala JM, Atchison ML . Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3). . J. Immunol. . 155 . 9 . 4330–8 . 1995 . 10.4049/jimmunol.155.9.4330 . 7594592 . free .
• Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D . FACT, a factor that facilitates transcript elongation through nucleosomes. . Cell . 92 . 1 . 105–16 . 1998 . 9489704 . 10.1016/S0092-8674(00)80903-4 . 11248520 . free .
• Dyer MA, Hayes PJ, Baron MH . The HMG domain protein SSRP1/PREIIBF is involved in activation of the human embryonic beta-like globin gene. . Mol. Cell. Biol. . 18 . 5 . 2617–28 . 1998 . 9566881 . 110641 . 10.1128/MCB.18.5.2617.
• LeRoy G, Orphanides G, Lane WS, Reinberg D . Requirement of RSF and FACT for transcription of chromatin templates in vitro. . Science . 282 . 5395 . 1900–4 . 1998 . 9836642 . 10.1126/science.282.5395.1900 .
• Kelley DE, Stokes DG, Perry RP . CHD1 interacts with SSRP1 and depends on both its chromodomain and its ATPase/helicase-like domain for proper association with chromatin. . Chromosoma . 108 . 1 . 10–25 . 1999 . 10199952 . 10.1007/s004120050347 . 12945778 .
• Spencer JA, Baron MH, Olson EN . Cooperative transcriptional activation by serum response factor and the high mobility group protein SSRP1. . J. Biol. Chem. . 274 . 22 . 15686–93 . 1999 . 10336466 . 10.1074/jbc.274.22.15686 . free .
• Orphanides G, Wu WH, Lane WS, Hampsey M, Reinberg D . The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins. . Nature . 400 . 6741 . 284–8 . 1999 . 10421373 . 10.1038/22350 . 1999Natur.400..284O . 4300397 .
• Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H . FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. . Mol. Cell . 5 . 6 . 1067–72 . 2000 . 10912001 . 10.1016/S1097-2765(00)80272-5 . free .
• Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H . A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. . Mol. Cell . 7 . 2 . 283–92 . 2001 . 11239457 . 10.1016/S1097-2765(01)00176-9 . free .
• Yarnell AT, Oh S, Reinberg D, Lippard SJ . Interaction of FACT, SSRP1, and the high mobility group (HMG) domain of SSRP1 with DNA damaged by the anticancer drug cisplatin. . J. Biol. Chem. . 276 . 28 . 25736–41 . 2001 . 11344167 . 10.1074/jbc.M101208200 . free .
• Santoro P, De Andrea M, Migliaretti G, Trapani C, Landolfo S, Gariglio M . High prevalence of autoantibodies against the nuclear high mobility group (HMG) protein SSRP1 in sera from patients with systemic lupus erythematosus, but not other rheumatic diseases. . J. Rheumatol. . 29 . 1 . 90–3 . 2002 . 11824977 .
• Roig J, Mikhailov A, Belham C, Avruch J . Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression. . Genes Dev. . 16 . 13 . 1640–58 . 2002 . 12101123 . 186374 . 10.1101/gad.972202 .
• Zeng SX, Dai MS, Keller DM, Lu H . SSRP1 functions as a co-activator of the transcriptional activator p63. . EMBO J. . 21 . 20 . 5487–97 . 2002 . 12374749 . 129072 . 10.1093/emboj/cdf540 .
• Keller DM, Lu H . p53 serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex. . J. Biol. Chem. . 277 . 51 . 50206–13 . 2003 . 12393879 . 10.1074/jbc.M209820200 . free .
• Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D . FACT facilitates transcription-dependent nucleosome alteration. . Science . 301 . 5636 . 1090–3 . 2003 . 12934006 . 10.1126/science.1085703 . 2003Sci...301.1090B . 26667338 .
• Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG . Regulation of alternative splicing by SRrp86 and its interacting proteins. . Mol. Cell. Biol. . 23 . 21 . 7437–47 . 2003 . 14559993 . 207616 . 10.1128/MCB.23.21.7437-7447.2003 .
• Tan BC, Lee SC . Nek9, a novel FACT-associated protein, modulates interphase progression. . J. Biol. Chem. . 279 . 10 . 9321–30 . 2004 . 14660563 . 10.1074/jbc.M311477200 . free .

Notes and References

1. Web site: Entrez Gene: SSRP1 structure specific recognition protein 1.
2. Tan BC, Lee SC . Nek9, a novel FACT-associated protein, modulates interphase progression . J. Biol. Chem. . 279 . 10 . 9321–30 . Mar 2004 . 14660563 . 10.1074/jbc.M311477200 . free .
3. Zeng SX, Dai MS, Keller DM, Lu H . SSRP1 functions as a co-activator of the transcriptional activator p63 . EMBO J. . 21 . 20 . 5487–97 . 15 Oct 2002 . 12374749 . 129072 . 10.1093/emboj/cdf540 .