Cell division cycle 34 ubiquitin-conjugating enzyme (CDC34)

Cell division cycle 34 ubiquitin-conjugating enzyme (CDC34) is an E2 ubiquitin-conjugating enzyme essential for the covalent attachment of ubiquitin to substrate proteins, a key process in cell cycle regulation and protein homeostasis[4][3][5]. CDC34 accepts ubiquitin from E1-activating enzymes and, in conjunction with E3 ligase complexes—especially cullin-RING ligases like SCF—catalyzes polyubiquitination (particularly Lys-48–linked chains) of target proteins, marking them for proteasomal degradation[3][4]. Notable substrates include cell cycle regulators such as cyclins, the cyclin-dependent kinase inhibitor p27^Kip1^, and the NF-κB inhibitor NFKBIA[4][3]. CDC34 is required for G1-S transition, DNA replication, and overall cell cycle progression[4][3]. Structural studies reveal CDC34 has unique features supporting its interaction with ubiquitin and E3 ligases, making its activity essential in controlling the timely degradation of regulators critical to proliferation and other signaling pathways[1][5]. CDC34 has been investigated as a potential anticancer target; small molecule inhibitors such as CC0651 selectively modulate its ubiquitin-transfer activity by binding allosteric sites, indicating druggability[6][8]. Loss or dysregulation of CDC34 function is implicated in cancer and other proliferative disorders[4][3].

Other names

Ubiquitin-conjugating enzyme E2 R1UBCH3UBE2R1E2-CDC34UBC3(E3-independent) E2 ubiquitin-conjugating enzyme R1Ubiquitin-conjugating enzyme E2-32 kDa complementingUbiquitin-protein ligase R1Cell division cycle 34 homologUbiquitin carrier protein

Inhibition of ubiquitin discharge by allosteric modulation, Inhibition/stabilization of E2~ubiquitin complex (prevents ubiquitin transfer to substrate protein)