日時：	October 19, 2023, Thu, 1:00pm
場所：	LiMe Bldg No.2, The 1st Floor Conference Room
演者：	Dr. Manabu Kurokawa Associate Professor Department of Biological Sciences Kent State University, USA
演題：	If the Mule isn’t kicking, it’s biting: various roles of HUWE1 in cancer and beyond

講演要旨

Ubiquitination is a protein post-translational modification in which the small peptide ubiquitin is covalently
conjugated to a substrate protein. Ubiquitination plays multiple key roles in cellular homeostasis by
affecting the activity or function of target proteins, altering protein subcellular localization, and promoting
protein degradation through the ubiquitin-proteasome pathway. Ubiquitination consists of three steps:
activation of ubiquitin by ubiquitin-activating enzymes (E1), transfer of ubiquitin from E1 to ubiquitinconjugating
enzymes (E2), and ligation of ubiquitin to a substrate lysine by E3 ubiquitin ligases. HUWE1
is a HECT-domain ubiquitin E3 ligase ubiquitously expressed in normal tissues. HUWE1 ubiquitinates a
wide range of cellular substrates, including p53, MYC, and MCL1. Given the diverse substrates, the in
vivo role of HUWE1 in human disease remains elusive. Our lab has previously demonstrated that oocytespecific
Huwe1 knockout renders female mice infertile, albeit via a p53-independent mechanism. We
have recently identified that HUWE1 is also a critical mediator of NAFLD (Non-Alcoholic Fatty Liver
Disease) etiology as liver-specific Huwe1 knockout rendered mice protected against hepatic steatosis
induced by age and diet. More recently, we also discovered that HUWE1 is a key tumor suppressor in
the p53-dependent DNA damage response. In this talk, various roles of HUWE1 in cancer and other
diseases will be discussed.

Contact: Takahiro Ito, Div. of Cell Fate Dynamics and Therapeutics, LiMe
takahiro.ito＊infront.kyoto-u.ac.jp; Ph: 075-751-4809（＊を＠へ変えてください）
医生物学研究所 伊藤貴浩（がん・幹細胞シグナル分野）