Molecular cloning and characterization of a RING‐H2 finger protein, ANAPC11, the human homolog of yeast Apc11p*

Abstract

Yeast Apc11p together with Rbx1 and Roc2/SAG define a new class of RING-H2 fingers in a superfamily of E3 ubiquitin ligases. The human homolog of Apc11p, ANAPC11 was identified during a large-scale partial sequencing of a human liver cancer cDNA library and partial characterization was performed. This 514 bp full-length cDNA has a predicted open reading frame (ORF) encoding 84 amino acids. The ORF codes for ANAPC11, the human anaphase promoting complex subunit 11 (yeast APC11 homolog), which possesses a RING-H2 finger motif and exhibits sequence similarity to subunits of E3 ubiquitin ligase complexes. In Northern blot hybridization with poly(A) RNA of various human tissues using radio-labelled ANAPC11 cDNA probe, we found strong signals detected in skeletal muscle and heart; moderate signals detected in brain, kidney, and liver; and detectable but low signals in colon, thymus, spleen, small intestine, placenta, lung, and peripheral blood leukocyte. The ANAPC11 gene is located at the human chromosome 17q25. ANAPC11 is distributed diffusely in the cytoplasm and nucleus with discrete accumulation in granular structures in all the cell lines (AML 12, HepG2, and C2C12) transfected. Expression level of ANAPC11 is found higher in certain types of cancer determined in the RNA dot blot experiment.

The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis of urothelial bladder cancer

“…ANAPC11, also known as APC11, is a core catalytic subunit of APC/C [44,45]. The APC/C is a nineteensubunit cullin-RING E3 Ub ligase, which binds with different cofactors to regulate the separation of sister chromatids from metaphase to anaphase [34,46].…”

The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer

“…ANAPC11, also called APC11, is a core catalytic subunit of APC/C [ 51 , 52 ]. APC/C is a nineteen-subunit cullin-RING E3 Ub ligase that binds with different cofactors to regulate the separation of sister chromatids during the progression from metaphase to anaphase [ 40 , 53 ].…”

Studies of the Ubiquitin Proteasome System

“…These are characterized by a small RING finger, a member of the cullin family of proteins and other linkers, regulatory components, and substrate recognition elements that are required for activity. Such multi‐subunit E3s include the SCF complexes, the anaphase‐promoting complex, or cyclosome, and the CBC E3s (Iwai et al, 1999; Skowyra et al, 1999; Chan et al, 2001). For most RING‐finger proteins, it is currently thought that the RING finger and substrate‐recognition element are encoded on a single polypeptide (Lorick et al, ).…”