Dr. Jianping Jin
The University of Texas Health Science Center at Houston
Department of Biochemistry and Molecular Biology
- Ubiquitin Signaling Pathway and DNA Damage Response
My laboratory is interested in studying genes involved in ubiquitylation and DNA damage responses. Two major research projects in the laboratory are:
1. System biology approaches to dissect new Uba6→Use1 ubiquitin signaling pathway
The first step of ubiquitylation is controlled by E1. It has been a few decades since the first E1 enzyme was identified, and it was believe that there was only one E1 for ubiquitin. Our recent discovery of a new E1 enzyme, Uba6, has opened a new era in ubiquitin research field. Uba6 is an essential gene for mouse development and only found in vertebrates and sea urchin. Uba6 transfers ubiquitin to its specific E2 enzyme, Use1, which is also limited in vertebrates and sea urchin. Serial biochemical and genetic experiments uncovered that Uba6 and Use1 constitute a unique activation and conjugation system for ubiquitin. Our lab takes a system biology approach to identify the downstream components of Uba6 and Use1, such as E3 ligases and substrates, and to characterize the biological function of this specific ubiquitin signaling pathway.
2. DNA damage checkpoint control by Cullin-RING ubiquitin ligases
Cullin-RING ubiquitin ligases (CRLs) constitute a super-family of multi-subunit E3 complexes. They consist of a ring finger protein, a cullin scaffold, an optional linker and a receptor subunit that usually has dozens of family members. CRLs control ubiquitylation of many important oncogenes and tumor suppressors, such as Cdc25A, c-Myc, c-Jun and p27. Emerging evidence indicates that CRLs play indispensable roles in the DNA damage checkpoint, cell division, DNA replication and repair, circadian rhythm, viral infection and chromatin remodeling etc. Mutations in components of CRLs have been found to be causative agents in certain cancers and other human diseases. Our laboratory focuses on the regulation of the DNA damage response through ubiquitylation by CRLs, particularly, by DCAF proteins that are the receptor subunits in CRL4 E3s.
Jin J, Li X, Gygi S, Harper JW (2007) Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. Nature, 447:1135-1138 (Editor's choice, Science, Vol. 2007, Issue 393, p. tw238; Research Highlights, Nature Reviews Molecular Cell Biology, 2007, Vol 8, p599).
Jin J, Arias EE, Chen J, Harper JW, Walter JC (2006) A family of diverse Cul4-Ddb1 interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Molecular Cell, 23:709-721 (Featured article).
Jin J, Ang XL, Shirogane T, Elledge S, Harper JW (2005) Identification of substrates for F-box proteins. Methods in Emzymology. 399(B):287-309.
Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Gene & Development. 18:2573-2580 (Bioinformatic Study on F-box Gene Family).
Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, Harper JW (2003) SCFβ-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes & Development. 17:3062-3074.