Sumo-Specific Protease 1 Controls Lymphoid Development Through Regulation of Sumoylation/Acetylation Switch In Stat5

<p>SUMOylation has emerged as an important regulatory mechanism for protein function. SUMO-specific proteases (SENPs) are essential for removing SUMO from conjugated proteins in many different systems, but the physiological functions of SENPs are poorly understood. STAT5 (Signal Transducer and Activator of Transcription 5) plays a critical role in the development of lymphoid cells. However, it is not known whether STAT5 is regulated by the SUMOylation pathway. Here, we showed that SUMOylated STAT5 is accumulated in SENP1^-/- lymphoid precursors. SENP1 deficiency results in severe defects in early T and B cell development, similar to that observed in mice harboring a complete inactivation of STAT5. Because STAT5 is SUMOylated and acetylated at the same lysine residue, SENP1 deficiency blocks STAT5 in the SUMOylation state, resulting in diminished STAT5 acetylation and phosphorylation, and defective lymphoid development. Thus, our results reveal a novel function of SENP1 in the regulation of early lymphoid development via an acetylation/SUMOylation switch in STAT5.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2011

Author dc:creator

• Nguyen, Thang Van

Contributors dc:contributor

• Edward T.H. Yeh, M.D.
• Chen Dong, Ph.D.
• Shao-Cong Sun, Ph.D.

• STAT5 SUMOylation Lymphoid development
• Life Sciences
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/162

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1189