1. Linkage of ubiquitin system between plant and mammalian
: Therapeutic Applications of
ubiquitin system for cancer
Plant Molecular Biology Lab Hani Kim

2. Ubiquitination
degradation of proteins via the ubiquitin-proteasome system(UPS) resulting apoptosis (programed cell death, PCD)
a type of post-translational modification
occurs when an ubiquitin molecule bonds to a substrate protein
This process involves three steps with specific groups of enzymes;
Activation with ubiquitin-activating enzymes (E1s)
Conjugation with ubiquitin-conjugating enzymes (E2s)
Ligation with ubiquitin ligases (E3s)

3. The ubiquitin system offers
several possibilities for therapeutic intervention.
Targeting the ubiquitin system in cancer therapy, Hoeller & Dikic, Nature 458, (2009)

4. Using the ubiquitin system in cancer therapy BY,
Targeting ubiquitin ligases
Targeting inhibitors of apoptosis
Deubiquitylating enzymes in cancer development
Targeting the proteasome in tumours
Interfering with recognition of ubiquitin
Targeting the ubiquitin system in cancer therapy, Hoeller & Dikic, Nature 458, (2009)

5. COP1 as E3 ligase
⇒ Model of UVR8 Action. UV-B photoreception by dimeric UVR8 forms monomers.
Marine, Nature reviews cancer, /nrc3271 (2012)
Gareth I. Jenkins Plant Cell 2014;26:21-37

6. Photomorphogenesis
: a change in plant development induced by specific kinds of light
and not dependent on photosynthesis
Phytochrome : a photoreceptor pigment with 2 interconvertible forms
Pr : the inactive form, absorbs red light at 660 nm
Pfr : the active form, absorbs far-red light at 730 nm

7. COP1 in plants,
Lau & Deng, null, Volume 17, Issue 10, 2012, 584–593

8. COP1 in plants, Arabidopsis Book. 2004; 3: e0074.1.
Proc Natl Acad Sci U S A Aug 23; 102(34): 12270–12275.

9. mouse and human COP1

10. Other E3 ligases regulate JUN stability

11. COP1-mediated degradation in cancers

12. Therapeutic targeting of COP1 signalling
COP1 as a tumour suppressor role in various cellular contexts, additional experiments are required to confirm.
- such as tissue-specific knock out in mice etc.
⇒ COP1 agonists could promote the degradation of COP1 targets, such as JUN or ETV1, in tumours expressing high levels of these oncogenes.
⇒ COP1 expression could be restored in cells lacking COP1 using an approach such as adenoviral-based gene delivery.