Control mechanisms in germ cells mediated by p53 family proteins

Abstract

Germ cells are totipotent and, in principle, immortal as they are the source for new germ cells in each generation. This very special role requires tight quality control systems. The p53 protein family constitutes one of the most important quality surveillance systems in cells. Whereas p53 has become famous for its role as the guardian of the genome in its function as the most important somatic tumor suppressor, p63 has been nicknamed 'guardian of the female germ line'. p63 is strongly expressed in resting oocytes and responsible for eliminating those that carry DNA double-strand breaks. The third family member, p73, acts later during oocyte and embryo development by ensuring correct assembly of the spindle assembly checkpoint. In addition to its role in the female germ line, p73 regulates cell-cell contacts between developing sperm cells and supporting somatic cells in the male germ line. Here, we review the involvement of the p53 protein family in the development of germ cells with a focus on quality control in the female germ line and discuss medical implications for cancer patients.

Utility of CD30, Ki‐67, and p53 in assisting with the diagnosis of mycosis fungoides with large cell transformation

“…TP53 (p53) is a tumor suppressor gene located on the short arm of chromosome 17, and has been described in a wide variety of carcinomas, sarcomas, and leukemias/lymphomas . It is often referred to as the “guardian of the genome” as p53 modulates the cell cycle and initiates apoptosis in response to DNA damage . Numerous studies have examined the relationship between p53 and mycosis fungoides with respect to disease progression, prognosis, and large cell transformation, although the results are not always consistent .…”

“…17 It is often referred to as the "guardian of the genome" as p53 modulates the cell cycle and initiates apoptosis in response to DNA damage. 18,19 Numerous studies have examined the relationship between p53 and mycosis fungoides with respect to disease progression, prognosis, and large cell transformation, although the results are not always consistent. [20][21][22][23] With the benefit of being a large tertiary referral center with an expert cutaneous lymphoma clinic with extensive clinical annotation, we aim…”

Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing

“…The p63 gene encodes two major isoforms of TAp63, one with the transactivation (TA) domain and the other, ∆N-p63 (N-terminal truncated), lacking the TA domain [84]. TAp63α is the main p63 isoform expressed in the nuclei of oocytes within primordial follicles [80,81,83].…”

“…Exposure to genotoxic agents such as radiation trigger a conformation change in TAp63α to its active tetrameric state, which in turn increases its DNA binding affinity and may ultimately cause apoptosis [85][86][87] and elimination of damaged oocytes ( Figure 2C). The presence of TAp63α in oocytes of immature follicles highlights the need for adequate surveillance mechanism to ensure only oocytes with complete DNA damage repair are recruited to ovulation [80,81,84].…”

“…(C) An interplay of dimeric to the tetrameric formation of TAp63α. Phosphorylation of TAp63α ultimately transforms the inactive dimeric form of TAp63α to the active tetrameric form (figure adapted from[84,85,87]).…”