March 30 2018
We would like to inform you that the 36th IRCMS Seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.
Date : April 3, 2018 (Tue)
Time : 16:00 - 17:00
Venue : 1F Meeting Lounge, International Research Center for Medical Sciences (IRCMS)
Speaker : Tatsuya Morishima M.D., Ph.D.
Postdoctoral Fellow, Department of Oncology, Hematology,
Immunology, Rheumatology and Pulmonology,
University Hospital Tübingen, Germany
"The role of NAMPT-NAD+-SIRTs pathway - mediated protein deacetylation in hematopoiesis and leukemogenesis"
Although extensively studied in the context of post-translational modification of DNA-binding histone proteins, deacetylation of non-histone proteins as received relatively little research attention. However, given that it occurs in evolutionarily conserved regions and is broadly distributed among different species, lysine deacetylation arguably has an impact on protein function. Nicotinamide phosphoribosyltransferase (NAMPT) - NAD+-sirtuins (SIRTs) pathway plays pivotal roles in wide range of cellular process via protein deacetylation activity of SIRTs.
Currently we are studying the role of this pathway in hematopoiesis and leukemogenesis and identified LMO2 and HCLS1 as target proteins of this pathway. LMO2 is an important transcription factor in early stage of hematopoiesis and leukemogenesis in T cell lymphoblastic leukemia (T-ALL). HCLS1 is a substrate of tyrosine kinase and elevated HCLS1 levels were reported in leukemia blasts. We found that NAMPT-NAD+-SIRTs pathway-mediated deacetylation was required for activation of these proteins. NAMPT/SIRT2 inhibition induced LMO2 protein acetylation and suppressed early hematopoiesis and proliferation of LMO2- expressing T-ALL cells. Expression levels of NAMPT and HCLS1 were elevated in chronic myeloid leukemia (CML) cells. NAMPT/SIRT1 inhibition induced HCLS1 protein acetylation and suppressed proliferation of CML cells. These new molecular mechanisms may explain the pathogenesis of hematopoietic diseases and targeting of protein deacetylation by NAMPT/SIRTs inhibition may be a potential novel therapy for leukemia.