Source

Mouse

Reactivity

Human;Mouse;Rat;Monkey

Background

The HECT domain-containing ubiquitin E3 ligase HECTH9 is critical for the ubiquitination and proteasomal degradation of many target proteins, and is involved in the regulation of a variety of cellular processes, including DNA replication and base excision repair, cellular proliferation, differentiation, and apoptosis. HECTH9 contains two Armadillo repeat-like domains, a ubiquitin-associated domain, a WWE domain, a well-conserved BH3 domain, and a catalytic HECT domain that facilitates ubiquitination of target proteins. HECTH9 has been shown to polyubiquitinate p53, Miz1, N-Myc, Mcl-1, Cdc 6, and DNA polymerase beta through K48-mediated linkage, thereby targeting these proteins for proteosomal degradation. The tumor suppressor protein ARF binds to and inhibits the uibiquitin ligase activity toward p53, resulting in stabilization of p53 and induction of apoptosis. HECTH9 has also been shown to polyubiquitinate c-Myc through K63-linkage, which is required for recruitment of p300, activation of c-Myc target genes, and induction of cellular proliferation. HECTH9 is overexpressed in colon, lung, and breast cancer. In addition, defects in HECTH9 result in mental retardation syndromic X-linked Turner type and mental retardation X-linked type 17 syndromes.

References

[1] Chen, D. et al. (2005) Cell 121, 1071-83.
[2] Yoon, S.Y. et al. (2005) Biochem Biophys Res Commun 326, 7-17.
[3] Yang, Y. et al. (2010) Proc Natl Acad Sci U S A 107, 13444-9.
[4] Zhao, X. et al. (2008) Nat Cell Biol 10, 643-53.
[5] Zhao, X. et al. (2009) Dev Cell 17, 210-21.
[6] Zhong, Q. et al. (2005) Cell 121, 1085-95.
[7] Hall, J.R. et al. (2007) Mol Biol Cell 18, 3340-50.
[8] Parsons, J.L. et al. (2009) EMBO J 28, 3207-315.
[9] Adhikary, S. et al. (2005) Cell 123, 409-21.
[10] Froyen, G. et al. (2008) Am J Hum Genet 82, 432-43.

Raw materials

Preparation Products