PROGENRA INC — Department of Health and Human Services SBIR Phase I: DESCRIPTION (provided by applicant): Many regulatory proteins are themselves tightly contr
PROGENRA INC — SBIR Phase I award from Department of Health and Human Services.
- Amount
- $224,974
- Agency
- Department of Health and Human Services · National Institutes of Health
- Program / Phase
- SBIR · Phase I
- Solicitation
- PA13-234
- NAICS
- —
- Place of performance
- PA
- Period
- —
Description
DESCRIPTION (provided by applicant): Many regulatory proteins are themselves tightly controlled by ubiquitin conjugating and deconjugating enzymes, whose dysfunctional forms are implicated in numerous diseases, including cancers. USP7, a deubiquitylating enzyme, regulates ubiquitylation and, thereby, stability of the E3 ligase HDM2, which in cells effects ubiquitylation and promotes proteasomal degradation of the tumor suppressor p53 as well as a number of other proteins such as FOXO4, PTEN and claspin. Thus, inhibiting USP7 can impact both p53 wild type and mutant tumors. In addition, by de-ubiquitylating and preserving the transcription factor Foxp3, USP7 increases T regulatory cell (Treg) mediated suppression of tumor-infiltrating T effector cells, the latter being associated with improved clinical outcome for many solid tumors, including lung cancers. Thus, USP7 functions to limit immune cell-mediated antitumor defenses. The observation that the accumulation of Foxp3+ Treg cells at the tumor or in d