WHSC2 explained

Negative elongation factor A is a protein that in humans is encoded by the WHSC2 gene.^{[1] [2]}

Function

This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation. WHSC2 encodes the NELF-A subunit of the NELF complex.^[3]

Interactions

WHSC2 has been shown to interact with RDBP.^[3]

Further reading

• Gutmajster E, Rokicka A . [Genetic determination of Wolf-Hirschhorn syndrome ] . Wiadomości Lekarskie . 55 . 11–12 . 706–10 . 2003 . 12715353 .
• Stevens M, De Clercq E, Balzarini J . The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention . Medicinal Research Reviews . 26 . 5 . 595–625 . Sep 2006 . 16838299 . 10.1002/med.20081 . 7168390 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Wright TJ, Ricke DO, Denison K, Abmayr S, Cotter PD, Hirschhorn K, Keinänen M, McDonald-McGinn D, Somer M, Spinner N, Yang-Feng T, Zackai E, Altherr MR . A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region . Human Molecular Genetics . 6 . 2 . 317–24 . Feb 1997 . 9063753 . 10.1093/hmg/6.2.317 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H . NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation . Cell . 97 . 1 . 41–51 . Apr 1999 . 10199401 . 10.1016/S0092-8674(00)80713-8 . 16855257 . free .
• Ping YH, Rana TM . DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation . The Journal of Biological Chemistry . 276 . 16 . 12951–8 . Apr 2001 . 11112772 . 10.1074/jbc.M006130200 . free .
• Mariotti M, Manganini M, Maier JA . Modulation of WHSC2 expression in human endothelial cells . FEBS Letters . 487 . 2 . 166–70 . Dec 2000 . 11150502 . 10.1016/S0014-5793(00)02335-8 . 5862862 . free .
• Ito M, Shichijo S, Tsuda N, Ochi M, Harashima N, Saito N, Itoh K . Molecular basis of T cell-mediated recognition of pancreatic cancer cells . Cancer Research . 61 . 5 . 2038–46 . Mar 2001 . 11280764 .
• Yamaguchi Y, Filipovska J, Yano K, Furuya A, Inukai N, Narita T, Wada T, Sugimoto S, Konarska MM, Handa H . Stimulation of RNA polymerase II elongation by hepatitis delta antigen . Science . 293 . 5527 . 124–7 . Jul 2001 . 11387440 . 10.1126/science.1057925 . 27068661 . free .
• Yamaguchi Y, Inukai N, Narita T, Wada T, Handa H . Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA . Molecular and Cellular Biology . 22 . 9 . 2918–27 . May 2002 . 11940650 . 133766 . 10.1128/MCB.22.9.2918-2927.2002 .
• Zollino M, Lecce R, Fischetto R, Murdolo M, Faravelli F, Selicorni A, Buttè C, Memo L, Capovilla G, Neri G . Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2 . American Journal of Human Genetics . 72 . 3 . 590–7 . Mar 2003 . 12563561 . 1180235 . 10.1086/367925 .
• Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H . Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex . Molecular and Cellular Biology . 23 . 6 . 1863–73 . Mar 2003 . 12612062 . 149481 . 10.1128/MCB.23.6.1863-1873.2003 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . Aug 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .

Notes and References

1. Wright TJ, Costa JL, Naranjo C, Francis-West P, Altherr MR . Comparative analysis of a novel gene from the Wolf-Hirschhorn/Pitt-Rogers-Danks syndrome critical region . Genomics . 59 . 2 . 203–12 . Jul 1999 . 10409432 . 10.1006/geno.1999.5871 .
2. Web site: Entrez Gene: WHSC2 Wolf-Hirschhorn syndrome candidate 2.
3. Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, Kim DK, Hasegawa J, Omori M, Inukai N, Endoh M, Yamada T, Handa H . Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex . Molecular and Cellular Biology . 23 . 6 . 1863–73 . Mar 2003 . 12612062 . 149481 . 10.1128/MCB.23.6.1863-1873.2003 .