We report a novel alkaline extractable protein of the sperm head that exclusively resides in the post-acrosomal sheath region of the perinuclear theca (PT) and is expressed and assembled in elongating spermatids. It is a protein that shares sequence homology to the N-terminal half of WW domainbinding protein 2, while the C-terminal half is unique and rich in proline. A functional PPXY consensus binding site for group-I WW domain-containing proteins, and numerous unique repeating motifs, YGXPPXG, are identified in the proline-rich region. Considering these molecular characteristics, we designated this protein PAWP for postacrosomal sheath WW domain-binding protein. Microinjection of recombinant PAWP or alkaline PT extract into metaphase II-arrested porcine, bovine, macaque, and Xenopus oocytes induced a high rate of pronuclear formation, which was prevented by co-injection of a competitive PPXY motif containing peptide derived from PAWP but not by co-injection of the point-mutated peptide. Intracytoplasmic sperm injection (ICSI) of porcine oocytes combined with co-injection of the competitive PPXY peptide or an anti-recombinant PAWP antiserum prevented pronuclear formation and arrested fertilization. Conversely, co-injection of the modified PPXY peptide, when the tyrosine residue of PPXY was either phosphorylated or substituted with phenylalanine, did not prevent ICSI-induced fertilization. This study uncovers a group I WW domain module signal transduction event within the fertilized egg that appears compulsory for meiotic resumption and pronuclear development during egg activation and provides compelling evidence that a PPXY motif of spermcontributed PAWP can trigger these events. The perinuclear theca (PT)3 of the mammalian sperm head is a condensed cytosolic structure layered between the sperm acrosome and nucleus and, continuing caudally, between the plasmalemma and nucleus. On a compositional basis, the PT can be subdivided into three structurally continuous regions, the subacrosomal layer, the outer periacrosomal layer on the outer aspect of the equatorial segment and the post-acrosomal sheath (PAS) (1, 2). Traditionally, PT has been considered as a cytoskeletal scaffold responsible for maintaining the overall architecture of the mature sperm head. However, recent studies indicate that the bulk of proteins making up the PT are not traditional cytoskeletal proteins but rather a variety of cytosolic proteins linked together and susceptible to extraction under different regimens (3). For example, alkaline extractable SubH2Bv, exclusive to the subacrosomal layer, is implicated in acrosome-nuclear docking during spermiogenesis (1). Salt-extractable non-nuclear somatic core histones, residing in the PAS, may be involved in stabilizing the chromatin of the decondensing sperm nucleus soon after oocyte entry (4, 5). The DTT salt or alkaline extractable calicin and cylicin II share a basic pI with the histones and bind to actin in vitro (6 -8). Detergentand salt-resistant fraction, "calyx fraction" of the PT, contain...

Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer, but recurrence occurs in most patients. Recent evidence suggests that CD133 þ cells are the cause of drug resistance and tumor recurrence. However, the correlation between chemotherapy and regulation of CD133 þ cells has not been investigated methodically. In this study, we revealed that CD133 þ lung cancer cells labeled by a human CD133