Covalent modification of all members of human cullin family proteins by NEDD8

Oncogene. 1999 Nov 18;18(48):6829-34. doi: 10.1038/sj.onc.1203093.

Abstract

Recently we found that NEDD8, a ubiquitin-like protein, was linked covalently to human cullin-4A (abbreviated Cul-4A) by a new ubiquitin-related pathway that is analogous to but distinct from the ligating system for SUMO1, another ubiquitin-like protein. However, it remained unknown whether the other five members of the family of human cullin/Cdc53 proteins are modified by NEDD8. Here we report that all Hs-Cul family proteins, such as Cul-1, Cul-2, Cul-3, Cul-4B, and Cul-5, in addition to Cul-4A, were modified by covalent attachment of NEDD8 in rabbit reticulocyte lysates. Moreover, by comprehensive Northern-blot analyses, we examined multiple tissue distributions of the messages for all Cul-family proteins, NEDD8, and the NEDD8-ligating system consisting of APP-BP1/hUba3, and hUbc12, which function as E1- and E2-like enzymes, respectively. The expressions of Cul-1, Cul-2, and Cul-3 resembled each other and were apparently correlated to those of NEDD8 and the NEDD8-ligating system in various human cells and tissues. However, the mRNA levels of Cul-4A, Cul-4B, and Cul-5 differed considerably from each other as well as from other Cul-family proteins. The enhanced expression of all Cul-family proteins except Cul-5 was observed in a variety of tumor cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • Gene Expression Regulation
  • Humans
  • NEDD8 Protein
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • NEDD8 Protein
  • NEDD8 protein, human
  • RNA, Messenger
  • Ubiquitins